The decision to centre emerging investigators rather than established luminaries is itself a statement about how science should evolve. The authors argue that researchers early in their careers are uniquely positioned to challenge prevailing assumptions, adopt interdisciplinary approaches and redirect priorities that may have calcified over decades. The resulting collection of perspectives spans an unusually wide technical range, from neoadjuvant immunotherapy in colorectal cancer to somatic mosaicism in healthy tissues, from the nervous system’s role in tumour progression to artificial intelligence models that predict cellular responses to genetic perturbation. Together, the six contributions sketch a research agenda that is more integrated, more prevention-focused and more computationally ambitious than anything the field has attempted before.

One thread running through the article is the remarkable maturation of cancer immunotherapy, particularly when treatment is moved earlier in the disease course. Myriam Chalabi, a medical oncologist and physician scientist at the Netherlands Cancer Institute in Amsterdam, has built her research programme around immunotherapy delivered in the neoadjuvant setting, using novel treatment combinations within innovative trial designs. The clinical evidence underpinning this shift is striking: recent work has demonstrated neoadjuvant immunotherapy in mismatch-repair-proficient colon cancers, while separate research has shown that non-operative management of mismatch repair deficient tumours can produce durable responses, in some cases allowing patients with rectal cancer to avoid surgery entirely. These results suggest that the immune system, when engaged before a tumour has been removed, can eliminate disease that conventional staging would consider established, and they raise the prospect of organ-preserving treatment as a realistic goal rather than an aspirational one.

Yet immunotherapy has also exposed the limits of tumour-centric thinking, and several of the authors argue that the next 25 years must focus on the host as much as the tumour. James L. Reading, an associate professor of cancer immunology at UCL who leads the Pre-cancer Immunology Laboratory, studies T cell-driven cancer interception — the idea of detecting and eliminating tumours before they become clinically invasive. His work builds on the discovery that reservoirs of stem-like CD8-positive T cells in tumour-draining lymph nodes sustain ongoing antitumor immune responses, and that conventional type I dendritic cells maintain pools of proliferative, tumour-antigen-specific TCF1-positive CD8-positive T cells in those same nodes. Understanding how these immune reservoirs are established and maintained during pre-invasive disease, he argues, could transform early detection from passive imaging into active, immune-guided interception, catching malignancy at a stage when cure rates approach certainty.

The genomic dimension of this preventive agenda is developed most fully by Tim H. H. Coorens, a group leader at the European Bioinformatics Institute who studies how somatic mutations accumulate in normal cells. Twenty-five years ago, cancer genomes were largely studied in isolation from the tissues that produced them. Today, it is clear that essentially every cell in the body accrues mutations over a lifetime, and that clones of mutant cells — some harmless, some pre-malignant — expand and compete in otherwise healthy tissue. Coorens contributed to the Somatic Mosaicism Across Human Tissues network, an effort to catalogue this variation systematically, and recent analyses have shown that age itself can distinguish selective clonal expansion from simple mutational causation in cancer genomes. Meanwhile, the real-world clinical utility of tumour whole-genome sequencing in solid cancers has now been demonstrated at scale, suggesting that comprehensive genomic profiling is moving from research luxury to standard of care. The conceptual shift is profound: cancer becomes not a foreign invader but one possible endpoint of a lifelong evolutionary process, and the levers for prevention may lie in the dynamics of normal tissue.

Perhaps the most visually striking frontier is cancer neuroscience. Leanne Li, a group leader at the Francis Crick Institute in London, combines cancer genetics with neurotechnologies to decipher the logic of interactions between tumours and the nervous system in mouse models. The field’s roots reach back more than a century to observations of nerves within tumours made using methylene blue vital staining, but modern cancer neuroscience has exploded in the past decade. Recent single-neuron sequencing has revealed how individual neurons are reprogrammed by pancreatic cancer, and comprehensive reviews have mapped the past, present and future of the discipline. Li also leads InteroCANCEption, a multidisciplinary team funded by Cancer Grand Challenges to tackle the broader question of how interoception — the body’s sensing and regulation of its own internal signals, a concept elaborated in modern neuroscience — shapes tumour initiation, growth and response to therapy. If tumours co-opt neural circuitry the way they co-opt blood vessels, then neuromodulatory drugs already approved for other conditions could become unexpected additions to the oncology arsenal.

Resistance to therapy, the stubborn core of cancer mortality, is the focus of Shensi Shen, associate professor at West China Hospital, Sichuan University. His work centres on drug-tolerant persister cells — a subpopulation of cancer cells that survives initial treatment not through genetic mutation but through reversible shifts in cell state. Reviews have traced the journey of persister cell biology from basic questions to clinical opportunities, and single-cell analyses have shown that genetically homogeneous cancer cells can diverge into multiple distinct clonal fates when exposed to the same drug. Shen’s particular interest is in layered translational control: the regulation of how messenger RNA is decoded into protein, which allows cancer cells to deploy hidden protein functions and switch states under therapeutic pressure. Because these transitions are non-genetic, they are also potentially reversible, which makes the persister state an attractive target for combination strategies designed to block the escape routes that tumours use to survive targeted therapy and immunotherapy alike.

Underpinning all of these biological questions is a computational revolution, examined by Ewa Szczurek, associate professor at the University of Warsaw and director of the Institute of AI for Health at Helmholtz Munich. Szczurek develops artificial intelligence models for molecular biology and medicine, and her perspective is notably sober about the current state of the field. While foundation models promise to predict how cells respond to genetic and pharmacological perturbations — an ambition exemplified by recent preprint work on state-based prediction of cellular responses — independent evaluations have shown that deep-learning-based gene perturbation effect prediction does not yet outperform simple linear baselines in many settings. Her message is that the next 25 years of AI in cancer research will be defined not by model size but by data quality, experimental validation and careful benchmarking. If the field heeds that warning, machine learning could genuinely accelerate target discovery and personalised treatment; if it does not, hype risks outrunning biology.

Woven together, the six perspectives describe a field in mid-revolution. The tumour-as-isolated-entity model is giving way to a systems view in which cancer is embedded in the evolutionary dynamics of normal tissues, the immune landscape of pre-invasive disease, the neural circuitry of the host body and the non-genetic plasticity of individual cells. Clinical paradigms are shifting in parallel: treatment is moving earlier, surgery is sometimes becoming optional, and molecular residual disease monitoring — exemplified by analyses of adjuvant osimertinib in resected EGFR-mutated lung cancer — is becoming a guide for post-operative decisions. The anniversary article also translates premalignant biology into strategies for intercepting non-small-cell lung cancer, illustrating how laboratory insight can be converted directly into prevention trials.

What emerges most clearly is a demand for interdisciplinarity as a structural principle rather than a slogan. The authors themselves embody it: a clinician designing immunotherapy trials, a bioinformatician decoding mutation accumulation, a neuroscientist engineering tools to interrogate tumour-nerve crosstalk, an immunologist chasing T cells before invasion, a molecular biologist tracking protein-level resistance and a computer scientist stress-testing the field’s newest models. Their collective wager is that the major killers of the next quarter-century will not be defeated by any single breakthrough but by the deliberate integration of genomics, immunology, neuroscience, developmental biology and computation — and by the willingness of a new generation to ask questions their predecessors did not think to ask.

Subject of Research: Emerging investigators' perspectives on the future priorities of cancer research over the next 25 years

Article Title: The next 25 years of cancer research: emerging perspectives and priorities

Article References: Chalabi, M., Coorens, T. H. H., Li, L., Reading, J. L., Shen, S., & Szczurek, E. (2026). The next 25 years of cancer research: emerging perspectives and priorities. Nature Reviews Cancer. https://doi.org/10.1038/s41568-026-00975-3

Image Credits: AI Generated

DOI: 10.1038/s41568-026-00975-3

Keywords: cancer research, Nature Reviews Cancer, immunotherapy, neoadjuvant therapy, somatic mosaicism, cancer neuroscience, cancer interception, drug-tolerant persister cells, tumour heterogeneity, whole-genome sequencing, artificial intelligence, early detection

The fellowship arrives at a moment when cancer research is increasingly shaped by connections between disciplines once treated as separate. Cancer is not only a disease of uncontrolled cell division; it is also a disease of altered gene regulation, disrupted communication between organs, immune dysfunction, metabolic rewiring, and persistent interactions with infectious agents. The new projects reflect that broader view. Several researchers will study the regulatory architecture that determines which genes are active, while others will develop technologies for mapping cell surfaces, identify hidden immune targets, or investigate the molecular machinery that makes tumors vulnerable to treatment. Together, the projects illustrate how fundamental biology can generate new routes toward prevention, diagnosis, and therapy.

Nicholas Aboreden, PhD, a Robertson Foundation Fellow working with Kimberly Stegmaier, MD, at Dana-Farber Cancer Institute, will investigate the poorly understood regulatory elements known as silencers. Although only about 2 percent of the human genome encodes proteins, much of the remaining sequence controls when genes are activated or repressed. Cancer cells frequently exploit enhancers to increase the expression of growth-promoting genes, but the mechanisms by which they use silencers to maintain malignancy remain less clear. Aboreden will map the regulatory genome of an aggressive pediatric leukemia marked by widespread gene repression. By identifying silencer elements essential for the leukemia state, he hopes to uncover vulnerabilities that can be targeted without damaging normal cells. His work could also clarify how gene repression contributes to other tumor types.

At the California Institute of Technology, Timmerman Traverse Fellow Shihui Chen, PhD, will explore the relationship between embryonic development and cancer. During early embryogenesis, genetically identical cells acquire different identities through carefully coordinated changes in gene expression. Similar developmental programs can be reactivated in cancer, allowing malignant cells to adopt abnormal states and invade surrounding tissues. Working with Magdalena Zernicka-Goetz, PhD, Chen will use mouse embryos to study CARM1, a gene regulator frequently overexpressed in human tumors. She will determine how CARM1 influences early cell-fate decisions and how the same regulatory logic may be hijacked during cancer initiation. At The J. David Gladstone Institutes, Timmerman Traverse Fellow Stephanie A. Gaglione, PhD, will pursue another underexplored dimension of tumor biology: cryptic antigens. These immune targets arise from unusual or noncoding regions of viral and tumor genomes and may be shared among patients. With Alexander Marson, MD, PhD, Gaglione will profile the antigens displayed by virally driven cancers and identify those capable of stimulating tumor-specific T cells. The results could support engineered T-cell therapies and cancer vaccines directed at targets that conventional approaches overlook.

Several Fellows are developing tools to see cancer biology at unprecedented molecular resolution. Connie and Bob Lurie Fellow Yi Hua, PhD, working with Alice Y. Ting, PhD, at Stanford University School of Medicine, plans to create SortID, a labeling technology based on an engineered bacterial enzyme. The method is designed to rapidly label exposed protein residues on cell surfaces without requiring researchers to attach pre-existing molecular tags. Hua will use SortID to map the surface of SLAMF7, a protein already considered an important therapeutic target in multiple myeloma. A detailed map of the protein’s interactions could reveal how tumor cells communicate with immune cells and identify opportunities for more selective immunotherapies. At Stanford, Lurie Fellow Zhuoran Li, PhD, will examine a different communication system: peptide hormones produced by the brain. Computational analyses suggest that the brain generates many previously unrecognized peptides, but their biological functions remain unknown. Working with Katrin J. Svensson, PhD, Li will identify these signals and determine how they influence appetite and whole-body metabolism, potentially revealing brain–tumor connections relevant to the well-being of cancer patients.

Other projects focus on the molecular systems that determine whether cells survive stress or become malignant. Devon Jeltema, PhD, at the University of California, Berkeley, will study how PARP enzymes modify RNA. PARPs are best known for chemically modifying proteins involved in DNA repair and cellular stress responses, and several PARP inhibitors are already used in cancer treatment. Jeltema’s research will investigate whether RNA modification represents an additional layer of immune defense against viral infection and cancer. By combining biochemical experiments with sequencing technologies, she aims to map modified RNA molecules and determine how these chemical marks alter immune signaling. At The Rockefeller University, Hope Funds for Cancer Research Fellow Jaejin Kim, PhD, will investigate how tissues retain molecular memories of inflammation. Conditions such as eczema, psoriasis, and inflammatory bowel disease can recur in the same anatomical locations, suggesting that stem cells preserve information about previous injury. Kim, working with Elaine Fuchs, PhD, will identify the genes and mechanisms that encode these memories and distinguish beneficial regenerative responses from persistent programs that increase cancer risk.

Metabolism is another central theme among the new fellowships. At The J. David Gladstone Institutes, Connie and Bob Lurie Fellow Rachael A. McMinimy, PhD, will study the pyruvate dehydrogenase complex, an enzymatic switch that determines whether glucose-derived carbon enters mitochondrial respiration. Normal cells often use mitochondria to generate energy efficiently, while many cancer cells redirect glucose through alternative pathways that support rapid proliferation and the production of cellular building blocks. McMinimy is investigating a newly identified mechanism that regulates the pyruvate dehydrogenase complex through selective protein degradation. Manipulating this pathway could force tumor cells to rely more heavily on mitochondrial metabolism and reduce their ability to grow. At Stanford, Robertson Foundation Fellow Gayathri Muthukumar, PhD, will examine post-translational modifications on cell-surface and intracellular membrane proteins. Tumor cells often carry unusually dense coatings of sugar molecules, known as glycans, which may alter signaling and help cancers avoid immune attack. Muthukumar will combine molecular mapping with precision genetic screens to determine which modifications promote oncogenesis. The findings could yield new therapeutic targets and diagnostic markers.

At the Massachusetts Institute of Technology, Timmerman Traverse Fellow Angelos Pistofidis, PhD, will investigate transcription termination factor 2, or TTF2, a protein involved in the mechanics of cell division. During mitosis, duplicated chromosomes must be compacted and accurately separated so that each daughter cell receives a complete genome. Alterations in TTF2 have been linked to defective chromosome segregation, DNA damage, and cell death, and many cancers appear to depend on the protein for survival. Pistofidis will use structural biology, biochemistry, and single-molecule biophysics to determine how TTF2 functions at the molecular level and identify weaknesses that could be exploited by future drugs. At Columbia University, National Mah Jongg League Fellow Christina A. Stephens, PhD, will study adhesion G protein-coupled receptors, or aGPCRs, a class of surface proteins increasingly associated with cancer. These receptors can influence cell growth and communication, but their activation mechanisms remain obscure. Using single-molecule microscopy and molecular dynamics simulations, Stephens will define how aGPCRs switch between inactive and active states and use that information to optimize therapeutic strategies against tumors carrying these receptors.

Two Fellows will investigate problems at the intersection of cancer and infectious disease. At The Rockefeller University, Timmerman Traverse Fellow Bailey Schultz, PhD, will study the growth and division of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis. Approximately one-quarter of the global population is estimated to have been infected with M. tuberculosis, and the disease kills more people than any other pathogen. Tuberculosis and cancer intensify one another: previous infection is associated with increased risk of some cancers, while tumors and chemotherapy can weaken immunity and make infection more dangerous. Some cancer immunotherapies may also reactivate dormant tuberculosis. Schultz will use genome-wide CRISPR-based approaches to identify bacterial genes that control cell growth and division, pointing to potential drug targets while anticipating genetic routes to antibiotic resistance. At Weill Medical College of Cornell University, Robertson Foundation Fellow Yang Su, PhD, will focus on c-MYC, a master regulator of cancer growth that has long been considered difficult to drug directly. Su will investigate a newly described form of chemical modification in c-MYC messenger RNA involving the addition of two methyl groups. Determining which enzyme installs the modification and how it changes c-MYC stability or activity could expose a new strategy for suppressing tumors driven by this oncogene.

The final project addresses the evolution of cancer within individual tumors. At Dana-Farber Cancer Institute, Robertson Foundation Fellow Shuya Wang, PhD, will work with David S. Pellman, MD, to understand how genome instability creates epigenetic diversity. Cancer cells in the same tumor can activate different genes, enabling some subpopulations to survive treatment, adapt to changing conditions, or become more aggressive. Wang will identify the genes and pathways that connect genomic instability with changes in the epigenome, the regulatory layer that controls gene activity without altering the underlying DNA sequence. Understanding how this heterogeneity arises could reveal ways to slow tumor evolution and treatment resistance. “There’s so much talent and excitement and passion and energy at this stage of a scientist’s career,” said current Damon Runyon-Timmerman Traverse Fellow Antonio J. LaPorte, PhD, emphasizing the importance of independent support for young investigators. Yung S. Lie, PhD, President and CEO of Damon Runyon, said the Foundation remains committed to backing researchers whose discoveries in prevention, diagnostics, and therapeutics might otherwise go unfunded. Since its founding in 1946, Damon Runyon says it has invested more than $491 million in nearly 4,100 scientists, including 13 researchers who later received Nobel Prizes.

Web References: http://damonrunyon.org/

Keywords: Damon Runyon Cancer Research Foundation, cancer research, postdoctoral fellows, cancer biology, cancer immunotherapy, gene regulation, epigenetics, cancer metabolism, tuberculosis, molecular therapeutics, CARM1, c-MYC, TTF2, cryptic antigens, RNA modification