Genomic testing for advanced cancer in the U.S. is hampered by unequal access across demographic groups and needs targeted policy solutions, researchers report.
Next-generation sequencing (NGS) was not carried out for the five most prevalent types of solid tumor among thousands of patients studied, the team revealed in JAMA Network Open.
And among those who did undergo this testing, wait time significantly varied according to race, insurance status, and practice setting.
“Our findings highlight the underrepresentation of certain patient demographics in tumor genomic profiling, revealing disparities in access to standard-of-care diagnostic modalities,” reported researcher Chadi Hage Chehade, MD, from the University of Utah, and coworkers.
“These results emphasize the need for healthcare policies to mitigate these gaps.”
Precision oncology has defined a new era in cancer treatment, enabling clinicians to tailor care based on the specific clinicogenomic features of a patient’s tumor, enabling more effective and less toxic treatment strategies.
NGS has emerged as a transformative technology, enabling comprehensive genomic profiling and uncovering alterations for targeted therapies.
To examine equity of care in the field, the researchers studied electronic health record data for patients with common advanced or metastatic cancers that spanned over 800 U.S. community and academic sites across the U.S. between 2018 and 2022.
The team examined time to first NGS testing and frequency of testing for 63,294 patients, including those with metastatic breast (19.1%), prostate (6.9%), pancreatic (9.7%), colorectal (21.6%), and non–small cell lung cancer (42.7%, NSCLC).
The median age in the group was 68 years and 53.7% was female. In terms of ethnicity, 2.7% were Asian, 10.0% were Black, 6.0% were Hispanic, 61.0% were White, and 20.3% were other races and ethnicities.
The frequency of testing increased over the four-year span across all cancer types, but by the final year of study up to 40% to 50% of patients were still not receiving NGS testing.
Results showed there were differential rates of testing and longer waiting times to NGS testing in some groups.
Patients with lower socioeconomic status (SES), non-Hispanic Black or Hispanic patients, those covered by Medicare, Medicaid, or other government programs, and those treated at an academic practice setting were significantly less likely to be tested in some of cancers than patients with high SES, who were non-Hispanic White, those covered by a commercial health plan, or those treated in community practice, respectively.
Among specific cancers, Hispanic patients were significantly less likely to be tested in metastatic breast or prostate cancer, and non-Hispanic Black patients were less likely to receive NGS in advanced NSCLC, metastatic colorectal or metastatic pancreatic cancer.
The findings highlight the need to improve access to standard-of-care diagnostic modalities and serve as a call to improve NGS testing rates nationwide, said Igor Makhlin, MD, in an accompanying Commentary article.
“While the accelerating pace of research and AI-driven technology is poised to herald the next generation of discoveries that translate into greater survival for patients with cancer, we cannot ignore the increased burden to stay up to date, largely born by community oncologists who manage a wide gamut of solid and liquid cancers,” he maintained.
“Creation and adoption of innovative strategies to support clinicians in implementing breakthrough advances into their practice regardless of zip code, practice site, or other factors will require a concerted effort by all relevant stakeholders, but closing this gap in GCC is absolutely necessary. Our patients are depending on us.”
A woman lies on an exam table, holding her partner’s hand tightly with anticipation, as a technician glides an ultrasound probe across her abdomen. On the screen, shifting staticky shadows resolve into a skull, a liver, and the flicker of a beating heart. For many families, this moment brings joy and relief. For others, it’s paralyzing, as doctors detect signs that something is wrong.
A single nucleotide change can cause neurodevelopmental delays and dimorphism, failing livers, and arrhythmia-ridden hearts. For decades, medicine could only identify these conditions, usually after birth. Prenatal screening has made it easier to detect progressive diseases like Duchenne muscular dystrophy, which degenerates and damages muscles before symptoms typically appear in childhood. But treating before birth could preserve tissue prior to the onset of irreversible deterioration.
Once unthinkable, genetic diseases can now be treated before birth. Fetal genetic intervention—including early screening, in utero gene therapy, stem cell transplantation, and even embryo editing—aims not just to diagnose disease but to correct it at its earliest stages. It is a rapidly advancing frontier, defined by technological promise and profound ethical questions.
It starts with detection
Jennifer Hoskovec, vice president of medical affairs at BillionToOne, has spent more than 20 years in prenatal genetics, an era dominated by risk assessment rather than intervention.
Historically, prenatal genetic screening has fallen into two main categories. Aneuploidy testing determines the risk of Down syndrome and other trisomies, sex chromosome abnormalities, and specific microdeletions. Screening is essential for these de novo mutations, which have no U.S. Food and Drug Administration (FDA)-approved genetic interventions. High-risk Down syndrome patients may receive a fetal echocardiogram, closer ultrasound monitoring, or tertiary care delivery with neonatal support. The standard practice is to screen, monitor, and manage.
Jennifer Hoskovec Vice President BillionToOne
The second category involves inherited recessive conditions like cystic fibrosis (CF), spinal muscular atrophy (SMA), and phenylketonuria. If both parents are carriers for the same genetic mutation, then their child has a 25% chance of being affected. Testing typically requires samples from both parents. If both are carriers, chorionic villus sampling (CVS) and amniocentesis can detect fetal abnormalities in the first and second trimesters, respectively. However, getting each partner to follow up is a major hindrance. “When people go through a screening process and are found to be carriers, less than 50% of their partners complete the testing,” Hoskovec told Inside Precision Medicine. “Half of U.S. carriers of these genetic conditions, whether common or rare, don’t know what it means for their pregnancy. That limits their ability to get diagnostic testing because we do not have all the pieces of the puzzle.”
Hoskovec’s team developed a workaround: a single-gene noninvasive prenatal test that analyzes fetal cell-free DNA (cfDNA) circulating in maternal blood. Around nine weeks into pregnancy, fragments of fetal DNA shed from the placenta can be sequenced and quantified. If a mother is a carrier for a condition like CF or sickle cell disease, the test looks for a second variant that is not present in her DNA and forms evidence of paternal contribution.
“For example, if a mother has [the] sickle cell trait, we first sequence the full beta-globin gene in the cfDNA, which contains a mixture of maternal and fetal DNA,” Hoskovec said. “We look for a second variant not present in the mother that would indicate paternal contribution.”
Despite not replacing CVS or amniocentesis, Hoskovec said the result is highly sensitive, identifying 95% of affected pregnancies in the conditions it covers. Crucially, it does not require partner testing. “This is a stepping stone,” Hoskovec explained. “This earlier detection will likely accelerate the field by increasing the number of eligible patients for clinical studies and registries, improving equitable access across ethnic groups, and advancing precision medicine in prenatal care.”
Avoiding germline editing
David H. Stitelman, MDr Associate Professor Yale-New Haven Children’s Hospital and Yale School of Medicine
As screening opens the door, fetal surgeons and gene therapy researchers are taking their first steps through it. A pediatric surgeon at the Yale School of Medicine, David H. Stitelman, MD, believes prenatal treatment has benefits. The fetus is small, so it can receive higher doses based on weight. As its immune system is still developing and more tolerant, stem cells are growing quickly and organs are still being formed, so problems can be fixed before they become permanent. Because the placenta exchanges oxygen, lung conditions like congenital diaphragmatic hernia can be treated during fetal life. But once a newborn takes a first breath, defective lungs can spell immediate crisis.
Fetal therapy is not new. Specialized centers have performed open fetal surgery for spina bifida and diaphragmatic hernia lung growth, and blood transfusions for fetal anemia dating back to the 1960s. What is new is the molecular toolkit. Stitelman’s lab is investigating gene editing methods that use the cell’s repair machinery to fix one- to three-base-pair DNA errors. Another team, led by pediatric and fetal surgeon Tippi MacKenzie, MD, at the University of California, San Francisco, is using viruses to replace genes for lysosomal storage diseases and fetal stem cells for alpha thalassemia.
Some diseases require only modest correction. In hemophilia, one percent normal clotting factor expression improves outcomes greatly. Increasing the expression of functional CFTR protein to 15% of wild-type levels may cure CF or at least make it manageable. Even a small number of liver cells corrected in hereditary tyrosinemia can boost growth and repopulate the organ. However, some situations, such as congenital cancer syndromes, may require nearly 100% correction. At present, Stitelman’s team achieves single-digit percentage editing in models of CF and beta thalassemia. “We’re in the optimization phase,” Stitelman told Inside Precision Medicine. “We are testing different nanoparticles and generations of editing strategies to incrementally reach therapeutic levels.”
Stitelman draws a clear ethical boundary: this is somatic editing, not germline editing. The aim is to treat the fetus as a patient, not to create heritable genetic changes. Instead of editing embryos in vitro, systemic therapeutic agents are delivered to avoid reproductive cell damage.
Unintended germline modification remains a concern. Editing a target gene could inadvertently disrupt developmental genes and affect future generations. But, Stitelman argues, medicine always carries risk. “In 1950, children with leukemia all died,” said Stitelman. “Today, some forms have a 98% long-term survival rate with chemotherapy. We know chemotherapy can cause germline mutations, yet we accept that risk because it saves lives. With gene editing, the issue is not zero risk but understanding and quantifying the risk. Ideally, there would be no measurable off-target effects. In the places we have examined, we have not seen off-target effects.”
One pregnancy, two patients
In a landmark trial in 2011 known as the Management of Myelomeningocele Study, investigators found that fetal surgery for severe spina bifida (myelomeningocele) achieved better results than postnatal repair. Surgically closing the spinal defect in utero improved motor function and reduced the need for shunting to relieve hydrocephalus. The benefit was so clear that the trial was stopped early and influenced how doctors treat structural birth defects.
Aijun Wang, PhD Professor University of California, Davis
At the University of California, Davis, biomedical engineer Aijun Wang, PhD, is working closely with fetal surgery pioneer Diana L. Farmer, MD, to evolve fetal intervention from heroic surgery to cellular and molecular therapy. Wang and Farmer launched the Cellular Therapy for In Utero Repair of Myelomeningocele (CuRe) trial, combining fetal surgery with stem cell transplantation. The goal is to not only close the spinal defect but also restore neural tissue and improve long-term function.
The lens that Wang has used to focus his research is fetal and maternal safety. “The fetus is the patient, but treatment inevitably carries some risk to the mother,” Wang told Inside Precision Medicine. “Open fetal surgery, in particular, poses significant maternal risk. Genetic treatments introduce additional uncertainties because the long-term effects of DNA modification are not fully understood. Safety must remain the highest priority.”
Genetic medicine delivery is a critical challenge for all life stages, but the stakes are particularly high for a developing fetus. In fetal development, targeting stem cell populations is especially important because these cells are highly active, proliferating, and migrating. If edited successfully at the right developmental window, their progeny will carry the correction. The problem would be if the edit was not just unsuccessful but detrimental.
Wang’s lab focuses on delivery systems, particularly lipid nanoparticles carrying mRNA-encoding gene-editing enzymes. For genetic manipulation and high-throughput screening, Wang’s lab utilizes mouse models. Fetal sheep are used for scaling and dosing, while human organoids are used for human-specific editing and functional outcomes.
“In our clinical work, we have engaged with the FDA and conducted extensive preclinical studies,” said Wang. “Using multiple complementary models is essential. Combining small animal models, large animal translational models, and human organoid systems provides a comprehensive framework for product development, from early screening to human-focused therapeutic design.”
Although the field is highly exciting and progressing rapidly, Wang warns against premature application, which could be dangerous. Safety, developmental biology, ethical considerations, and multidisciplinary collaboration are all essential. “Despite the excitement in the field, we must proceed cautiously,” said Wang. “There is strong potential for correcting specific mutations, especially point mutations, using precise gene editing approaches such as base editing. However, safety evaluation must precede rapid clinical application.”
Effective progress requires a village of physicians, surgeons, researchers, engineers, and ethicists working together. Scientific progress requires caution, responsibility, and thorough evaluation before clinical use.
The earlier, the better
If fetal intervention treats a diagnosed fetus, embryo editing operates even earlier—at the blastocyst stage in in vitro fertilization (IVF). Norbert Gleicher, MD, a fertility specialist known for treating some of the oldest and most difficult IVF patients in the United States, approaches genetic technologies with caution. Due to biological mosaicism, sampling limitations, and his belief that many abnormal embryos self-correct or develop normally, Gleicher opposes preimplantation genetic testing for aneuploidy.
Norbert Gleicher, MD Founder & Medical Director Center for Human Reproduction
But when it comes to single-gene diseases, he sees a different calculus. Couples with recessive mutations may have one-in-four embryos affected, and in dominant or X-linked diseases, half may carry the mutation. For patients who produce few embryos—especially older women—discarding affected embryos can mean losing precious chances at pregnancy. “If you can cure an embryo rather than discard it,” Gleicher told Inside Precision Medicine, “that makes a lot of sense.”
For single-gene diseases, Gleicher believes genetic editing with CRISPR or other platforms is the most straightforward intervention. He points to the 2025 work at the Children’s Hospital of Philadelphia on Baby KJ as a recent milestone. Even partial correction, which Gleicher believes is likely the case with Baby KJ—though no liver biopsies have been extracted—can transform prognosis. Gleicher said, “Correcting some cells was enough to clinically cure the baby, at least for the time being, from symptoms of a disease that historically kills affected children within a few years. However, we do not know whether the treated baby, who likely still has many affected cells, might become symptomatic again later in life.”
To Gleicher, success in a newborn is all the more reason to apply genetic intervention to fetal stages. “If this can be successful in a full human being, imagine how much easier it would be at the blastocyst stage, or even earlier at the cleavage stage, when the embryo consists of only six to eight cells,” said Gleicher. “If [CRISPR] is applied at that point, correcting those six to eight cells would mean that all their daughter cells would also be corrected. The result would be a normal baby at birth. That is the much stronger argument in this case.”
Just because something is possible, it doesn’t necessarily mean it should be done, and Gleicher establishes a clear ethical boundary. Editing to prevent a devastating single-gene disease is one thing. Editing for traits—eye color, intelligence, polygenic risk scores—is another. Polygenic predictions explain only a fraction of trait variance, and embryo implantation itself is uncertain. To him, offering polygenic selection in IVF is not only scientifically dubious but also ethically troubling. “It is surprising that professionals, particularly in genetics, would suggest such an approach,” said Gleicher. “It is worse than snake oil, because while snake oil may occasionally work by accident, this carries a real risk of causing serious harm.”
A pretty penny
What ultimately restricts fetal genetic intervention is timing. Early screening increases experimental trial eligibility, and early treatment may preserve organ development before irreversible damage. In conditions like CF and SMA, where postnatal gene therapies are expensive and delivered after injury, fetal intervention could change outcomes. Frontline screening can identify high-risk pregnancies at 11 weeks without family history or ethnicity, expanding trial access.
Yet, fetal genetic interventions require specialized teams, advanced delivery systems, counseling, and long-term follow-up. Without careful planning and reimbursement policies, only a few top-tier centers could progress, widening the gap. Ethical scrutiny remains inseparable from progress. Innovation must balance maternal risk, fetal benefit, and future consequences with safety, appropriate use, and clear limits. As prenatal care shifts from prediction to prevention, restraint and evidence will determine its future.
Jonathan D. Grinstein, PhD, North American editor for Inside Precision Medicine, investigates the most recent research and developments in a wide range of human healthcare topics and emerging trends, such as next-generation diagnostics, cell and gene therapy, and AI/ML for drug discovery. He is also the host of the Behind the Breakthroughs podcast, featuring people shaping the future of medicine. Jonathan earned his PhD in biomedical science from the University of California, San Diego, and a BA in neural science from New York University.
Unlike static, rules-based systems, AI agents can learn, adapt, and optimize processes dynamically. As they interact with data, systems, people, and other agents in real time, AI agents can execute entire workflows autonomously.
But unlocking their potential requires redesigning processes around agents rather than bolting them onto fragmented legacy workflows using traditional optimization methods. Companies must become agent first.
In an agent-first enterprise, AI systems operate processes while humans set goals, define policy constraints, and handle exceptions.
“You need to shift the operating model to humans as governors and agents as operators,” says Scott Rodgers, global chief architect and U.S. CTO of the Deloitte Microsoft Technology Practice.
The agent-first imperative
With technology budgets for AI expected to increase more than 70% over the next two years, AI agents, powered by generative AI, are poised to fundamentally transform organizations and achieve results beyond traditional automation. These initiatives have the potential to produce significant performance gains, while shifting humans toward higher value work.
AI is advancing so quickly that static approaches to task automation will likely only produce incremental gains. Because legacy processes aren’t built for autonomous systems, AI agents require machine-readable process definitions, explicit policy constraints, and structured data flows, according to Rodgers.
Further complicating matters, many organizations don’t understand the full economic drivers of their business, such as cost to serve and per-transaction costs. As a result, they have trouble prioritizing agents that can create the most value and instead focus on flashy pilots. To achieve structural change, executives should think differently.
Companies must instead orchestrate outcomes faster than competitors. “The real risk isn’t that AI won’t work—it’s that competitors will redesign their operating models while you’re still piloting agents and copilots,” says Rodgers. “Nonlinear gains come when companies create agent-centric workflows with human governance and adaptive orchestration.”
Routine and repetitive tasks are increasingly handled automatically, freeing employees to focus on higher value, creative, and strategic work. This shift improves operational efficiency, fosters stronger collaboration, and generates faster decision-making—helping organizations modernize the workplace without sacrificing enterprise security.
This content was produced by Insights, the custom content arm of MIT Technology Review. It was not written by MIT Technology Review’s editorial staff. It was researched, designed, and written by human writers, editors, analysts, and illustrators. This includes the writing of surveys and collection of data for surveys. AI tools that may have been used were limited to secondary production processes that passed thorough human review.
This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.
The one piece of data that could actually shed light on your job and AI
Within Silicon Valley’s orbit, an AI-fueled jobs apocalypse is spoken about as a given. Now even economists who have downplayed the threat are coming around to the idea.
Alex Imas, based at the University of Chicago, is one of them. He believes that any plan to address AI’s impact will depend on collecting one vital piece of data: price elasticity.
This article is from The Algorithm, our weekly newsletter giving you the inside track on all things AI. Sign up to receive it in your inbox every Monday.
Four things we’d need to put data centers in space
In January, Elon Musk’s SpaceX applied to launch up to 1 million data centers into Earth’s orbit. The goal? To fully unleash the potential of AI—without triggering an environmental crisis on Earth.
This story is part of MIT Technology Review Explains, our series untangling the complex, messy world of technology to help you understand what’s coming next. You can read more from the series here.
The must-reads
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 Trump has again proposed major cuts to US science and tech spending He wants to slash nearly every science-focused agency. (Ars Technica) + If Trump gets his way, the US could face a costly brain drain. (NYT $) + Top research talent is already fleeing the country. (Guardian) + Basic science deserves our boldest investment. (MIT Technology Review)
2 Sam Altman lobbied against AI regulations he publicly welcomed A bombshell report reveals many OpenAI insiders don’t trust him. (The New Yorker $) + Some have called him a sociopath. (Futurism) + OpenAI’s CFO fears it won’t be IPO-ready this year.(The Information $) + A war over AI regulation is brewing in the US. (MIT Technology Review)
3 NASA’s Artemis II has broken humanity’s all-time distance record The astronauts have flown farther than any humans before them. (BBC) + Their mission includes MIT-developed technology. (Axios)
4 Chinese tech firms are selling intel “exposing” US forces It comes from combining AI with open-source data.. (WP $) + AI is turning the Iran conflict into theater. (MIT Technology Review)
5 War is pushing countries to ditch hyperscalers Driven by Iran naming tech giants as military targets. (Rest of World) + No one wants a data center in their backyard. (MIT Technology Review)
6 OpenAI, Anthropic, and Google have united against China’s AI copying They’re sharing information on “adversarial distillation” (Bloomberg $)
7 Anduril and Impulse Space are working on Trump’s “Golden Dome” They’re developing space-based missile tracking for the project. (Gizmodo)
8 OpenAI has urged California to probe Elon Musk’s “anti-competitive behavior.” It accuses Musk of trying to “take control of the future of AGI.” (Reuters $) + And claims he coordinated attacks with Mark Zuckerberg. (CNBC) + A former Tesla president has revealed how he survived working for Musk. (WP $)
9 DeepSeek’s new AI model will run on Huawei chips It’s expected to launch in the next few weeks. (The Information $)
10 Memes have nuked our culture Internet “brain rot” has escaped our phones to take over everything. (NYT $)
Quote of the day
“I must say, it was actually quite nice.”
—Astronaut Victor Glover tells President Donald Trump what it was like when Artemis II was out of communication with the rest of humanity, The New York Times reports.
One More Thing
PABLO ALBARENGA
Inside the controversial tree farms powering Apple’s carbon-neutral goal
In 2020, Apple set a goal to become net zero by the end of the decade. To hit that target, the company is offsetting its emissions by planting millions of eucalyptus trees in Brazil.
Apple is betting that the strategy will lead to a greener future. But critics warn that the industrial tree farms will do more harm than good.
A place for comfort, fun and distraction to brighten up your day. (Got any ideas? Drop me a line.)
+ Japan’s automated bike garage is a cyclist’s dream come true. + This deep dive into bird behavior reveals the secrets of their dining habits. (Big thanks to reader Terry Gordon for the find!) + The first photo from the Artemis astronauts vividly captures the glow of our atmosphere. + There’s a new contender for the world’s most gorgeous website: RobertDeNiro.com.
WASHINGTON — The Food and Drug Administration used the president’s budget to propose policies aimed at encouraging domestic development and manufacturing of drugs.
FDA Commissioner Marty Makary has said the agency needs “giant, big ideas” to counter China’s dominance in early-stage clinical development of drugs. Among the FDA’s ideas are proposals to make it easier to run early-stage trials in the U.S. and to hand an advantage to U.S.-based generics manufacturers.
The Trump administration has been using a variety of policy levers to try and bring drug manufacturing to the U.S. For example, many of the brand drugmakers that struck deals to lower U.S. prices also promised to increase domestic manufacturing, under the threat of tariffs.
“It took me years to find out that what I was dealing with was OCD!”
This is a phrase all too often repeated by people living with obsessive compulsive disorder. Currently, individuals live with OCD for an average of 7 years (Dell’Osso et al, 2019) before they even receive a diagnosis, all while symptoms may intensify and daily life often becomes increasingly constrained.
Clinicians, researchers, and advocates have long raised this concern. What has been missing is clear data behind how many people with OCD in the U.S. are missed in clinical settings or are not receiving the most effective treatment.
When the International OCD Foundation undertook this analysis, the scale of the problem became unmistakable. Millions of people in America are currently struggling with OCD without the most effective treatment.
Well established prevalence rates for OCD indicate that nearly 10 million people in America — roughly 3% (Ruscio et al, 2010; Stein et al,2025; Ringeisen et al, 2025) — will have OCD at some point in their lives. Yet our findings suggest that 75% of them are never even identified, and up to 95% aren’t receiving the most effective treatment for the disorder.
In our analysis, we discovered significant systemic breakdowns at several key points of a patient’s journey: screening, diagnosis, referral, and treatment.
Screening and Diagnosis: Receiving a clinical diagnosis is an important step toward recovery as it promotes understanding and opens paths to effective treatment. Yet our findings suggest that this crucial initial step is missing for many millions of people. Of the 10.4 million patient records reviewed in our analysis, only 0.51% received a formal OCD diagnosis, far below the 3% expected prevalence rate.
Referral to appropriate care: After a diagnosis is obtained, a handoff to appropriate care is needed to keep the patient from falling out of the treatment pathway. Here, too, we found an alarming gap within our sample: more than 72% of patients identified as having OCD did not receive a referral for cognitive-behavioral therapy (CBT), the most effective treatment for OCD.
Effective Treatment: Decades of research has established Exposure and Response Prevention (ERP) therapy, a specific form of CBT, as the most effective, first-line therapy for OCD. Yet, an astounding 95-98% of people with OCD had not received ERP treatment. Even when people seek help — and even when they are diagnosed — the vast majority never reach the treatment most likely to help them recover.
What We Can Do About It
The breakdowns seen in each step of the care pathway reinforce the focus of IOCDF’s Vision 2030, our five-year strategy to address the systemic barriers that keep effective OCD treatment out of reach.
While the findings are stark, they illuminate many opportunities for change:
Identify symptoms earlier by implementing routine OCD screening in primary healthcare and mental health settings.
Support clinicians in better understanding and treating OCD by expanding training in assessment, diagnosis, and evidence-based treatment modalities.
Help people receive care that works by strengthening adherence to existing professional treatment guidelines.
Increase the number of people with OCD who receive effective treatment by supporting affordable access to ERP and other evidence-based therapies.
Let people know they’re not alone by raising accurate public awareness of what OCD really is — and that it is treatable.
Vision 2030 outlines how the IOCDF is committing its resources, partnerships, and expertise toward advancing these priorities — by increasing awareness and community, expanding access to effective treatment, and advancing research. Together, these efforts are designed to work in concert, improving clinical training, implementing screening for early identification, strengthening pathways from diagnosis to care, and increasing the likelihood that people receive evidence-based treatment.
At the same time, the scale of the problem revealed in this report makes clear that progress depends on collective action across the field. Clinicians, health systems, educators, researchers, policymakers, advocates, and people with lived experience all have a role to play. Together, these efforts can help ensure that people with OCD reach effective treatment sooner, reducing years of unnecessary confusion and distress.
How You Can Help
Join us in building better access to effective treatment for people with OCD:
Share America’s OCD Care Crisis and other IOCDF resources with your clinicians and healthcare professionals.
Donate to the IOCDF to support training programs, advance research, and raise awareness of OCD and related disorders.
The current state of treatment for OCD in the U.S. is sobering, but it is not the end of the story. OCD is treatable, recovery is possible, and change can happen as awareness grows and access expands. With continued effort, the gap between how many are struggling and how many receive effective care can begin to close. A brighter future is possible — and we can build it together.
References
Dell’Osso, B., Benatti, B., Grancini, B., Vismara, M., De Carlo, V., Cirnigliaro, G., Albert, U., & Viganò, C. (2019). Investigating duration of illness and duration of untreated illness in obsessive compulsive disorder reveals patients remain at length pharmacologically untreated. International Journal of Psychiatry in Clinical Practice, 23(4), 311–313. https://doi.org/10.1080/13651501.2019.1621348
Ruscio, A. M., Stein, D. J., Chiu, W. T., & Kessler, R. C. (2010). The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Molecular Psychiatry, 15(1), 53-63. https://doi.org/10.1038/mp.2008.94
Stein, D. J., Ruscio, A. M., Altwaijri, Y., Chiu, W. T., Sampson, N. A., Aguilar-Gaxiola, S., Al-Hamzawi, A., Alonso, J., Chardoul, S., Gureje, O., Hu, C., Karam, E. G., McGrath, J. J., Navarro-Mateu, F., Scott, K. M., Stagnaro, J. C., Torres, Y., Vladescu, C., Wciórka, J., Xavier, M., … Kessler, R. C. (2025). Obsessive-compulsive disorder in the World Mental Health surveys. Research Square, rs.3.rs-6090427. https://doi.org/10.21203/rs.3.rs-6090427/v1
Ringeisen, H., Edlund, M., Guyer, H., Dever, J., Carpenter, L., Olfson, M., First, M., Geiger, P., Liao, D., Peytchev, A., Carr, C., Chwastiak, L., Dixon, L. B., Monroe-Devita, M., Scott Stroup, T., Swanson, J., Swartz, M., Gibbons, R., Stambaugh, L., Bareis, N., … Mental Health and Substance Use Disorders Prevalence Study Consortium (2025). Prevalence of past-year mental and substance use disorders, 2021-2022. Psychiatric Services (Washington, D.C.), 76(8), 720–728. https://doi.org/10.1176/appi.ps.20240329
IOCDF Training & Resources for Clinicians
When clinicians have easier access to best practices in OCD diagnosis and treatment, more people can receive effective care. The IOCDF’s Training Institute offers evidence-based programs for clinicians at every stage of practice, including:
A robust, on-demand webinar catalog (CE-eligible!) covering fundamentals, modalities, related disorders, and comorbidities. The catalog includes access to the free webinar, OCD Basics.
IOCDF’s Training Institute offers intensive workshops and events, consultation groups, and more for clinicians of every level.
Professional Members at the IOCDF join a nationwide network of committed professionals, are eligible for listing on our Resource Directory, and have access to special pricing for Training Institute offerings.
Background: Periodontitis is a chronic gum disease affecting approximately 42% of adults aged 30 years and older in the United States. Training dental students to accurately diagnose and manage periodontitis is a critical component of dental education and clinical care. Recent advances in large language models offer new opportunities to support both domains, yet their performance in periodontal diagnosis remains largely unexplored, particularly for newer models such as GPT-5. Objective: This study conducted an exploratory evaluation of GPT-5’s ability to stage and grade periodontitis. Methods: A total of 25 publicly available clinical cases explicitly reporting periodontitis stage and grade were identified through Google and PubMed searches. Each case description was entered into GPT-5 using a zero-shot prompting approach to assess guideline-based reasoning without exemplar conditioning. The model’s predictions were compared with the published reference diagnoses. Performance was measured using accuracy, 95% CI, unweighted Cohen κ, and weighted Cohen κ. Results: Across these cases, GPT-5 showed marked class-dependent performance and a tendency to overestimate disease severity. Grading performance was notably imbalanced, with high recall for grade C but substantially lower discrimination for grade B. GPT-5 achieved a staging accuracy of 68% (95% CI 48.4%-82.8%) and a grading accuracy of 77.3% (95% CI 56.6%-89.9%), with corresponding Cohen κ values of 0.454 (95% CI 11.0%-75.6%) and 0.179 (95% CI −15.8% to 63.8%), respectively. While staging performance showed fair agreement beyond chance, the low κ for grading indicates poor agreement and limited reliability in distinguishing periodontal disease severity. Conclusions: These findings suggest that although GPT-5 demonstrates potential for guideline-based periodontitis staging and grading, its current diagnostic performance, particularly for periodontitis grading, limits its use in clinical assessment and educational training. Meaningful application in periodontal diagnosis and training will require substantial improvements in reliability and rigorous validation in larger, more diverse, and prospectively collected datasets.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/840839ff7cd91d4050f40346f98235a6" />
Although immunoglobulin G (IgG) normally protects the body against pathogens, it can become problematic in many autoimmune diseases like lupus, rheumatoid arthritis, Graves’ disease, myasthenia gravis, and Sjögren’s disease.
“In these conditions, the immune system is creating defective IgGs—called autoantibodies—that are no longer fighting infections,” explained Eric Venker, MD, PharmD, CEO of Immunovant. “Instead, they are attacking a part of your normal functioning body and causing dysfunction.”
Leonard L. Dragone, MD, PhD Disease Area Leader Johnson & Johnson Innovative Medicine.
Historically, autoimmune conditions have been challenging to treat because therapies like steroids rely on broad immune suppression, noted Leonard L. Dragone, MD, PhD, disease area leader of autoantibody and rheumatology at Johnson & Johnson Innovative Medicine. These non-specific approaches are often inconsistently effective and lead to adverse side effects.
“For many autoimmune diseases, there is a need for more targeted strategies that address disease-causing autoantibodies directly, rather than broadly suppressing the immune system,” emphasized Dragone. Beginning in 1998, the U.S. Food and Drug Administration (FDA) approved infliximab, a tumor necrosis factor (TNF)-α inhibitor, for the treatment of Crohn’s disease. This marked the first approval of a monoclonal antibody for the treatment of a chronic condition. Since then, targeted therapies for autoimmune diseases have expanded to address cytokine signaling pathways (TNF-α, IL-6, IL-17, IL-23), Janus kinase (JAK–STAT) signaling, and immune cell surface markers (CD20).
Another such targeted strategy involves an emerging drug class called FcRn blockers, which are now showing considerable promise in the treatment of certain autoimmune diseases.
FcRn blockers, which typically consist of monoclonal antibodies or antibody fragments, work by blocking the function of a protein receptor called FcRn (neonatal Fc receptor). This prevents IgG recycling, thereby reducing IgG levels in the body.
FcRn maintains levels of IgG in circulation by preventing IgG degradation in the lysosomes of cells. However, FcRn drugs block this pathway.
Venker compares FcRn inhibitors to cholesterol-lowering drugs such as statins. “LDL is the disease-causing agent that healthcare providers target to prevent many cardiovascular diseases. Likewise, in the case of FcRn blockade, we are aiming to lower IgG. We believe that deeper IgG reduction may provide improved results.”
As of early 2026, the FDA has approved three FcRn inhibitors for the treatment of myasthenia gravis, a chronic autoimmune disorder affecting up to 100,000 people in the U.S. Efgartigimod (approved in 2021), rozanolixizumab-noli (approved in 2023), and nipocalimab-aahu (approved in 2025) all work by reducing pathogenic IgGs associated with the disease.
Myasthenia gravis results from harmful antibodies (anti-AChR or anti-MuSK) produced by the immune system that interfere with signaling in the neuromuscular junction.
“With FcRn blockers, it is exciting to know that there is now a targeted mechanism for patients around the world with autoimmune diseases caused by an IgG autoantibody,” said Venker.
Tackling Graves’ disease
In Graves’ disease, an IgG autoantibody called thyrotropin receptor antibody (TRAb), which targets the thyroid-stimulating hormone (TSH) receptor of the thyroid, is produced. The condition, which is the most common cause of hyperthyroidism, causes elevated heart rate, shakiness, irritability, muscle weakness, and weight loss.
“TRAb is an IgG antibody, but it is a badly behaving one that is basically hijacking the thyroid system,” noted Venker. “It doesn’t serve any purpose that is normal at all.”
Mark A. Lupo, MD Founder and Medical Director Thyroid & Endocrine Center of Florida
Unfortunately, the toolkit for treating Graves’ disease hasn’t changed much since 1950, when the FDA approved the drug methimazole, said Mark A. Lupo, MD, founder and medical director of the Thyroid & Endocrine Center of Florida.
Methimazole is an anti-thyroid drug that slows down the production of thyroid hormones. Although Graves’ patients benefit from anti-thyroid drugs, Lupo estimates a 50% relapse rate within two years of discontinuing these drugs.
Other options for treating Graves’ disease include surgical removal of the thyroid or the use of radioactive iodine to induce destruction of the thyroid gland. However, these approaches result in permanent hypothyroidism, and patients typically require lifelong thyroid hormone replacement after treatment.
Because TRAb is an IgG, FcRn drugs represent a potential autoimmune solution for Graves’ disease. Like all FcRn blockers, they may work by decreasing TRAb recycling and lowering TRAb levels.
Lupo highlights Immunovant’s recent proof-of-concept study of an FcRn inhibitor for Graves’ disease, the first such study for the condition. “Despite the small number of patients (around 25), the results from this study suggest a potential, durable remission six months off treatment,” said Lupo.
While study participants experienced an increase in total IgG levels following treatment, TRAb levels remained low over a six-month period. The thyroid also decreased in size. “To see TRAb levels down six months off the study drug caught the attention of the endocrine thyroid community,” noted Lupo.
“What was unexpected was that TRAb, the disease-causing antibody, stayed down for many months after stopping the investigational therapy,” added Venker.
“I think we are overdue for a new option in Graves’ disease that could help break some of these methimazole cycles and potentially address not the innocent thyroid gland but the underlying immune system issues,” concluded Lupo.
But are they safe?
Venker recalls that safety was an initial concern with FcRn inhibition. After all, these drugs work by reducing IgG, an essential part of the immune system. “Any time you are using an autoimmune drug that potentially suppresses your immune system, you have to think about going too far. Am I going to cause an infection or weaken the immune system?
“So far, this investigational drug has demonstrated a safety profile we expected, and appears positive,” noted Venker. “That makes sense mostly because FcRn blockade is pretty targeted.”
“Although there are no head-to-head comparative safety trials yet, most clinicians and principal investigators view FcRn blockers as relatively safe,” added Lupo. “There are FcRn blockers on the market, and they have demonstrated a good safety record in patients.” The most common side effect tends to involve injection site reactions with either intravenous or subcutaneous delivery.
Preventing fetal exposure
During pregnancy, maternal antibodies—called alloantibodies—can cross the placenta and attack the organs and tissues of the fetus, explained Dragone.
A distinguishing feature of Johnson & Johnson’s nipocalimab is its pH-independent binding to FcRn. This allows it to bind with high affinity in the placenta, a low-pH environment.
The drug is currently showing potential in the treatment of two alloimmune diseases of pregnancy: hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT), said Dragone. These conditions can arise during alloimmunized pregnancies, when the pregnant person’s immune system forms alloantibodies against fetal red blood cells (HDFN) and/or fetal platelets (FNAIT). Importantly, published data on nipocalimab suggest minimal transfer of the drug to the fetus or infant. “Therapies like nipocalimab offer a blueprint for how precision medicine can expand to include pregnant people, a population that has historically been excluded from drug development,” noted Dragone. “Our approach with nipocalimab has the potential to change how we think about treating autoantibody-driven diseases in people of childbearing age.”
Nipocalimab (IMAAVY®) and other FcRn blockers bind to FcRn receptors and reduce levels of both normal and harmful IgG antibodies.
The FDA has granted a fast track designation to nipocalimab for both FNAIT and HDFN, and Phase III studies are underway to further investigate the drug in both diseases.
Expanding indications
“There are probably 20 trials out there for FcRn blockers, and many are likely to work,” noted Venker. “There are a ton of potential new indications under investigation, including rare diseases that have been ignored historically.”
He notes that Immunovant’s pipeline alone includes potential indications in endocrinology (Graves’ disease), rheumatology (rheumatoid arthritis, Sjögren’s disease, and cutaneous lupus erythematosus), and neurology (myasthenia gravis and chronic inflammatory demyelinating polyneuropathy).
Venker stresses that no FDA-approved solutions exist for Sjögren’s disease, which affects as many as four million Americans. The condition causes severe dry eyes and mouth, fatigue, and joint and muscle pain. Immunovant and Johnson & Johnson are conducting clinical trials to evaluate FcRn blockers for the disease.
Hani Houshyar, PhD Strategy Team Lead argenx
Meanwhile, argenx’s FcRn inhibitor efgartigimod has been used in 19,000 people worldwide for myasthenia gravis and other autoimmune conditions, said Hani Houshyar, PhD, FcRn asset strategy lead for argenx.
“However, we believe myasthenia gravis is just the beginning,” she said. As of 2026, the company has active clinical trials to test the drug’s effectiveness in additional autoimmune diseases with high unmet medical need, like myositis, Sjögren’s disease, ocular myasthenia gravis, systemic sclerosis, Graves’ disease, and autoimmune encephalitis.
UCB’s rozanolixizumab was the first FcRn blocker to be approved for the treatment of generalized myasthenia gravis in adults who are positive for anti-AChR or anti-MuSK antibodies, who together account for approximately 90% of cases, said Omar Sinno, MD, UCB’s U.S. medical strategy lead of rare disease. So far, the drug has been approved in the U.S., Canada, the EU, Australia, Switzerland, China, Turkey, and Korea.
Omar Sinno, MD Medical Strategy Lead, UCB
Rozanolixizumab is administered via a convenient subcutaneous infusion rather than intravenously. The company’s long-term studies demonstrate robust IgG reductions (up to 75%) with sustained benefit across multiple treatment cycles. UCB is also investigating rozanolixizumab as a potential treatment for a rare autoimmune condition called myelin oligodendrocyte glycoprotein antibody-associated disease.
Finally, Johnson & Johnson’s nipocalimab is in mid-to-late-stage studies for Sjögren’s disease, lupus, warm autoimmune hemolytic anemia, and chronic inflammatory demyelinating polyneuropathy.
Drugs in development
Viridian Therapeutics is currently investigating two FcRn inhibitors, VRDN-006 and VRDN-008, said Steve Mahoney, president and CEO. Both candidates are designed as subcutaneous products that can be conveniently self-administered by the patient.
Steve Mahoney President and CEO Viridian Therapeutics
VRDN-006 is an Fc fragment in Phase I trials, while VRDN-008 is made up of an Fc fragment and an albumin-binding domain designed to prolong IgG suppression. Mahoney notes that VRDN-008 showed a longer half-life and more sustained IgG reduction than efgartigimod in a high-dose, head-to-head study in non-human primates.
Clinical trial results of VRDN-008 in healthy volunteers are expected later in 2026. “What we believe differentiates VRDN-008 from other FcRn inhibitors is a longer half-life, which has the potential to support less frequent dosing for patients to enhance convenience,” said Mahoney.
Although three FcRn blockers are currently FDA-approved to treat myasthenia gravis in the U.S., Venker notes that Immunovant is continuing to investigate the condition with the company’s follow-on FcRn candidate, imeroprubart (IMVT-1402).
In Immunovant’s proof-of-concept study for Graves’ disease, TRAb stayed low even six months after the investigational treatment was discontinued. But how long will this effect last? “We don’t know that yet because our randomized trials with IMVT-1402 are ongoing,” Venker said. “However, Graves’ disease has given us the first hint that FcRn drugs may be able to put certain autoimmune conditions into permanent remission.”
Viridian’s VRDN-006 (top) is an Fc fragment, whereas VRDN-008 (bottom) is made up of an Fc fragment and an albumin-binding domain designed to prolong IgG suppression.
“A key question for autoimmune disease, the holy grail, so to speak, is whether we can reset the immune system so the person can function normally without medication for the rest of their lives,” he added.
Finally, argenx is developing ARGX-213, a next-generation FcRn inhibitor engineered to extend half-life and sustain IgG reduction.
“Looking ahead, FcRn inhibition represents an increasingly important approach across IgG-driven disease,” noted Sinno. “By selectively reducing pathogenic IgG, these agents enable more targeted autoimmune care. And as clinical experience with FcRn inhibition grows, treatment paradigms may shift toward earlier intervention.”
Tiffany Yesavage, PhD is a freelance writer from Denver, Colorado.
As a postdoctoral researcher at the University of Pennsylvania, Haijiao Liu, PhD, helped advance tumor-on-a-chip technology, a feat of bioengineering that mimics the microenvironment of malignant human tumors. Led by Dan Dongeun Huh, PhD, a Penn Engineering professor and trailblazer of organ-on-a-chip technology, Liu and his team explanted lung adenocarcinoma tumors onto the transparent chips to test their perfusion with chimeric antigen receptor (CAR) T cells. Their findings were published in October in Nature Biotechnology, with Liu as first author.
Now on paternity leave in Toronto, Liu spoke with Lindsey Leake about the implications of this work, the challenges inherent to tumor-on-a-chip studies, and his plans to launch a lab of his own this fall.
Q: Walk me through the creation of the tumor-on-a-chip. What went into its design?
Haijiao Liu: It’s essentially inspired by the need for alternative tumor models. This is speaking to the traditionally used animal tumor models and some existing in vitro tumor models, especially for the study of immunotherapies.
For example, when I started at Penn around 2018, Penn Medicine was pioneering this immunotherapy called CAR T-cell therapy, which is basically aiming to harness the patient’s own immune system, specifically the patient’s own T cells, to help fight the cancer. Penn Medicine was demonstrating huge clinical success using this CAR T therapy to treat blood cancers, such as leukemias and lymphomas. In a huge contrast to this, the solid cancer arena has seen a limited response from this new immunotherapy. So there’s this great need to study why this has not been successful, and that comes down to the consensus that the solid tumor has this really complex microenvironment.
In the category called tumor-on-a-chip, people try to control the cultural environment, the biochemical and biophysical environment of tumor cell cultures. We can use this for simple drug testing—see how the tumor growth will be affected or how effectively they can be killed. However, these existing tumor-on-chip or in vitro tumor models are still very simple. They don’t usually recreate or reproduce the complex structure of the human solid tumors that I described, like where they often include complex vessel networks.
I took the lead to address the need and the challenges of reproducing and then investigating, or probing, the dynamic interactions between those CAR T cells and human solid tumors entirely in vitro.
Q: How does the vascularization work on the chip?
Liu: It took several years to start, from the idea of building this more advanced tumor-on-a-chip technology toward proving it’s actually useful. I started by focusing on this one aspect, which is the CAR T-cell trafficking and their functions after they traffic to fight the tumors, and that will involve the recreation of the structural interface between the tumor and this complex vascular network that’s present in human tumors.
I was inspired by in vivo tumor transplantation, where traditionally, people take human tumors and then transplant them in a bulk, intact format into animal models. So my idea was, if we want to focus more on the human biology, if we want to engineer this entirely in vitro, how about we design a vascular bedding, like a miniature living model?
We basically took advantage of the self-assembly capability of human-sourced endothelial cells, combined with certain stromal fibroblasts, or stromal cells. With a bit of optimization, engineering, tweaking, then we can allow them to form capillary-like vascular networks in our engineered models.
Q: What are the advantages of recreating the tumor microenvironment in this way? That is, is the Petri dish becoming obsolete in cancer research?
Liu: The unique advantage of this way of engineering is to have a higher level of control over the structures of the tissue-tissue interface that we can build. For example, we can engineer different culture chambers. We can engineer different access windows with this model. That allows us to construct, step by step, the vascular bedding and then the tumor transplantation. Also, by forming these perfusable vessels—by the way, we can provide the infusion and flow of the CAR T cells, just like they are infused and flow in the patient—that gives us the leverage to reconstruct, probe, and then control these tissue functions in a highly precise manner.
Q: How did you and your colleagues at Penn explore CAR T-cell activity on the chip?
Liu: We first used different functional assays, like immunostaining and ELISA (enzyme-linked immunosorbent assay) assays, to characterize how the CAR T cells are doing and how they are interacting with the tumors in our engineered model. Then we disassembled this engineered tissue to extract all the cells for flow cytometry, to further characterize their functional phenotypes.
With the help of our collaborators and other people in the lab, I took advantage of this engineered model of vascular tumors interacting with CAR T cells for multi-omics analysis. For example, I was able to extract all the cells and send them for single-cell RNA seq[uencing]. We were able to look at the gene expressions of each individual cell from all the cell types that we included in this model. In this way, we have almost like a superpower to probe and read into how each cell—including the CAR Ts and tumors and the vessels—how they are responding and interacting with each other at the molecular gene levels. This is so powerful that it helped me to discover novel interactions between these parties and also new druggable targets.
The message is that through the development of this more advanced tumor-on-a-chip technology—combined with advanced multi-omics analytics and advanced computational analysis—we were able to provide this powerful in vitro technology to apply to accelerate the development of cell therapies, such as the CAR T immunotherapies for cancer, but also other complex diseases.
Q: What are the overall implications of this latest research?
Liu: With a growing understanding of human biology at the cellular and tissue levels, I think we’re seeing that our ability to engineer and design biological systems is also growing. More than ever, we have these advances in the ability to precisely construct, investigate, and then eventually control very complex tissue functions, and even organ functions. For example, our demonstrated tumor-on-a-chip technology is like presenting a miniature sandbox; we can literally see and predict the battlefield of CAR T therapy in cancer.
If we combine these advanced engineering technologies with emerging technologies in spatial multi-omics and the unprecedented productivity of the AI revolution, we will be able to accelerate the understanding of more complex human biology and extract more biological insights, and then apply that to accelerate the development of safer and more efficacious drugs and therapies, such as immunotherapies in cancer.
Q: What are the limitations of organ-on-chip technology that need to be overcome?
Liu: I think there are challenges on two fronts. The first limitation is the lack of complexity. We’re claiming that what we just published is a sufficiently complex system for us to deeply probe and understand the dynamics of CAR T tumor interactions. Still, if we’re speaking next level of translational power or potential, then we need to pursue a higher complexity that incorporates the missing but critical components from in vivo.
The other side of the coin is that if you make this engineered model more complex, you make it more challenging to reproduce or to scale up or to translate to other labs. But also, that points to an opportunity and growing room for translation, to standardize every single step, from the construction to the analysis of these engineered models, and to automate these processes as much as possible.
Q: What do you envision for your new lab?
Liu: I have a lot of things I want to do. I’m eager to establish my own team. The overarching and the unifying theme of the new lab will be to develop the next generation of in vitro complex tissue models, or I call it assembloid tissue models. Assembloid basically means there’s a stem cell-based, three-dimensional complex tissue model that intentionally incorporates different cell types, to emulate the critical tissue-tissue interactions that determine the tissue- and organ-level functions. I still need to make a big decision where the lab could be; it could be in Canada and it could also be in China.
Q: What impact might tumors-on-a-chip have on the future of precision medicine?
Liu: It’s attracting a lot of attention from biologists and clinicians who are heavily focused on using the traditional tissue models—animal models, for example, or the simple dish cultures—for their studies of interest. So the biggest impact I can foresee with our technology is that now it’s more mature. I can see it being gradually, and maybe quickly, adapted into more traditional biological labs, to help them dissect the complex biological questions they’re asking, or to accelerate the evaluation of the exciting new drugs or therapies they’re developing. Overall, I can see that accelerate this development pipeline of new drugs and therapies in precision medicine.
Lindsey Leake is an award-winning, independent health reporter based outside Washington, D.C. She spent 15 years as a staff journalist at outlets including Fortune, the USA TODAY Network and Sinclair Broadcast Group. She holds an MA in Science Writing from Johns Hopkins University, an MA in Journalism and Digital Storytelling from American University and a BA from Princeton University.
