Medicine is approaching a decisive year. In a year-ahead outlook, Nature Medicine asked leading researchers to identify the clinical trials they believe could shape medicine in 2026. Their selections span infectious diseases, cardiovascular care, cancer, autoimmune disorders, rare diseases and neurological repair.

Taken together, the expert-nominated trials point to a shift in ambition. Many aim for longer-lasting protection, durable disease control or entirely new therapeutic approaches. Not all will succeed. But a high number of late-stage trials will report around 2026. That makes the year a critical test of whether recent scientific advances can translate into clinical impact.

Infectious disease moves back to centre stage

Several trials highlighted in Nature Medicine’s expert selection focus on infectious diseases that still impose a heavy global burden.

Tuberculosis remains one of the world’s deadliest infections. Adolescents and adults face the highest risk, yet existing vaccines offer limited and waning protection. A large late-stage trial now tests a next-generation TB vaccine designed to close that gap. If it succeeds, it would mark the most significant advance in TB prevention in decades.

HIV research is also shifting away from daily drug regimens. One trial evaluates long-acting broadly neutralising antibodies that aim to suppress the virus even after standard antiretroviral therapy stops. Early findings suggest that some patients may maintain viral control for extended periods. That raises questions about how HIV care could evolve.

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Lassa fever, rabies, long Covid

Other expert-selected trials target neglected but high-risk pathogens. One early-stage study evaluates a dual vaccine against Lassa fever and rabies, diseases endemic in parts of West Africa. The trial reflects growing concern about epidemic preparedness, health-system resilience and biosecurity.

Long Covid remains one of the pandemic’s most difficult legacies. Patients report persistent fatigue, post-exertional symptom worsening and multi-system dysfunction. Clear treatment options remain scarce. Among the trials highlighted in Nature Medicine’s outlook is a large late-stage study testing repurposed drugs that aim to reduce inflammation and improve microvascular function.

The trial also reflects a broader shift in approach. Patients helped shape the study design and intervention choices. Results expected in 2026 may clarify whether long COVID can move toward evidence-based treatment, or whether uncertainty will continue to dominate care.

Inflammation reshapes cardiovascular prevention

Cardiovascular disease remains the leading cause of death in Europe and globally. Prevention strategies, however, have long focused almost exclusively on cholesterol.

Several expert-selected trials now test whether targeting inflammation can reduce cardiovascular events independently of lipid lowering. One programme evaluates inhibition of interleukin-6 in patients with residual inflammatory risk. Another examines whether reducing lipoprotein(a), a genetically driven cholesterol particle, lowers rates of heart attack and stroke.

If successful, these trials could reshape screening practices and prevention guidelines. They also raise policy questions about access, cost and how health systems prioritise risk reduction.

Long-resistant cancers…

Few cancers illustrate unmet need as starkly as pancreatic cancer. Nearly all pancreatic tumours share mutations in the same gene, KRAS. For decades, that target resisted drug development. One late-stage global trial highlighted by Nature Medicine’s experts now tests a broad RAS inhibitor against standard chemotherapy in metastatic disease.

The study will assess whether targeted inhibition improves survival with fewer side effects. A positive result would mark the first widely applicable targeted therapy for this cancer type.

Other trials aim to extend immunotherapy into settings where benefits remain limited. In metastatic breast cancer, a large study tests whether combining a cell-based immunotherapy with immune checkpoint inhibition improves outcomes in heavily pre-treated patients.

…and therapies beyond cancer

Technologies developed for oncology are increasingly moving into autoimmune and rare diseases. In myasthenia gravis, an autoimmune disorder that causes muscle weakness, one trial tests an mRNA-based CAR-T cell therapy. The approach temporarily reprogrammes immune cells rather than permanently altering DNA. Early results suggest durable symptom control without broad immune suppression.

Another expert-selected study applies precise gene editing to chronic granulomatous disease, a rare inherited immune disorder. Researchers correct the faulty gene in a patient’s own stem cells before reinfusion. Early findings point to long-term disease control.

These approaches raise difficult questions about scalability and commercial viability. Patient populations are small. Development costs are high. Reimbursement remains uncertain. Yet for patients with limited options, the clinical stakes remain high.

Regenerative medicine

Stem-cell therapies remain one of medicine’s most contested frontiers. Among the trials highlighted in Nature Medicine’s outlook is a human clinical study delivering a patient’s own bone-marrow-derived stem cells intravenously and nasally. The approach aims to improve neurological function. Conditions under study include stroke, Parkinson’s disease and traumatic brain injury.

Supporters report functional gains. Critics point to variability and limited mechanistic understanding. Results expected in the coming years will help determine whether regenerative approaches can move toward broader clinical acceptance.

A year of answers, and hard choices

By the end of 2026, medicine should have clearer answers to several long-standing questions.

Can infectious diseases be prevented more durably?
Will inflammation become a core cardiovascular target?
Can cell and gene therapies extend safely beyond cancer?
Can patients with long COVID finally access evidence-based care?

As Nature Medicine’s expert selection shows, not every trial will succeed. Many will fail. Still, the range and ambition of studies reaching late-stage testing suggest that 2026 will test whether years of scientific investment can deliver tangible change for patients, and whether health systems can absorb it.

This article draws on clinical trials highlighted in Nature Medicine’s 2026 expert outlook on studies likely to shape future medical practice.