How can we better map the evolution of cancer to help improve precision therapy? What role does age play in the development of cancer? What can be learned from tissues that rarely get cancer? What understudied targets are worth studying? These are among the questions that fascinate the early-career researchers selected as the 2025 NextGen Stars by the American Association for Cancer Research (AACR). During the AACR Annual Meeting 2025, April 25-30 in Chicago, each one of the 11 members of this 2025 class will present some of the findings that have most excited them as they seek answers to key questions in cancer research.
Established in 2014, the NextGen Stars program offers an exciting opportunity to increase visibility and to support the professional development of early-career scientists who submit outstanding applications to the AACR Annual Meeting. Selected graduate students, postdocs, and assistant professors are given the chance to share their discoveries in Major Symposia and Advances sessions. But prior to the meeting, Cancer Research Catalyst asked each of this year’s AACR NextGen Stars a question of our own: Where do you hope your research is in five years?
Read on to learn about their various areas of research and what you might expect to hear from them at the AACR Annual Meeting 2025 (click their names for details about their sessions) and in the future.
Charting the Unknown in Cancer
Exploring the spatial biology of cancer is not a new concept, but Anand Jeyasekharan, MBBS, PhD, of the National University of Singapore, wants to popularize a new name: cancer cartography.
“In order to navigate the world, we first needed to make maps of as much of the world as possible,” Jeyasekharan said. “The idea is the same for cancer.”
Jeyasekharan wants to use technologies like spatial transcriptomics and immunofluorescence to first collect as much information about as many tumor types in as many situations as possible. Following this cataloging exercise, the next step would be to turn to artificial intelligence to help understand the relationships between everything they observe in these two-dimensional tumor maps. Eventually, Jeyasekharan would like to incorporate real-world data from patients to further inform these maps and provide a clearer understanding of what treatments will work best for different patients.
“Every patient who goes through the cancer journey is almost an ‘experiment’ in itself,” he explained. “The doctor gives a drug, we hope for the best, and sometimes it works and sometimes it doesn’t. These real-life experiments provide therefore an opportunity to use spatial biology approaches to create the next generation of diagnostics, so we can better answer questions about which patients should receive which medications.”
The tumor microenvironment also has uncharted areas. Anniina Färkkilä, MD, PhD, is mapping it, using spatial multiomics technologies, to study the mechanisms that enable cancer cells to evade the immune system. Similar to Jeyasekharan, Färkkilä, of the University of Helsinki, envisions a future where treatments could be more personalized to patients based on what is discovered about the spatial interactions of cells within the tumor microenvironment. However, she explained this will require advances in technology and computational modeling to not only capture these spatial interactions but to recognize patterns that can help inform treatment.
“For example, ovarian cancer is a disease marked by significant inter- and intra-patient heterogeneity, meaning that the same treatment approach may not be effective for all patients,” Färkkilä explained. “Within the next five years, I aim to contribute to a deeper understanding of which specific types of immunotherapies are most effective in particular patient subsets and at which time, whether used alone or in combination with other agents. To achieve this, detailed translational analyses are essential, particularly those derived from ongoing clinical trials, to guide treatment strategies.”
Another unknown area of cancer has fascinated John Prensner, MD, PhD, of the University of Michigan, who is exploring the dark proteome. While much of what we know about the cancer genome is tied to the approximately 20,000 protein-coding genes that have been discovered, Prensner is interested in the thousands of unstudied microproteins that cancer cells produce. By investigating the dark proteome, Prensner hopes to uncover new therapeutic targets like CircFAM53B-219aa, one of the first proteins discovered from the dark proteome and a target in a new clinical trial testing a dendritic cell vaccine for breast cancer.
“Within five years, I want to see more clinical trials based on dark proteome therapies as well as to better understand mutational variants and their impact on the dark proteome,” Prensner said. “I would also like to see the determinants of the cancer dark proteome be revealed so we can answer the question: Why is it that cancer cells make these unique peptides in the first place?”
What’s Age Got to Do With Cancer?
Elvin Wagenblast, PhD, of the Icahn School of Medicine at Mount Sinai, is also using advanced technologies to map the development of cancer to answer a slightly different question: Why do blood cancers emerge so early in life? Researchers have found that some childhood blood cancers, such as leukemia, can develop from mutations that occur before birth, and Wagenblast wants to understand what are the early events that lead to this and what insights can be gleaned to help treat or prevent cancer.
“Early hematopoiesis remains poorly understood in humans, particularly how distinct waves of blood cell production shape the foundation for lifelong blood formation,” Wagenblast explained. “In five years, I hope for a deeper understanding of how human developmental biology influences blood cancer. Advancements in single-cell multiomics, spatial transcriptomics, and genome engineering will enable more precise mapping and functional characterization of these developmental processes.”
Meanwhile, Stephanie Xie, PhD, of the University Health Network Princess Margaret Cancer Centre, is interested in why some people develop cancer as they age while others do not. She is exploring the characteristics of human hematopoietic stem cells (HSCs), and how metabolic and inflammatory stress responses in these cells could contribute to clonal hematopoiesis and cancer risk.
Using hematopoiesis models, Xie and her colleagues recently discovered that inflammatory stress in a subset of cells replicated the transcriptional and epigenetic changes that happen during aging. They called these HSC inflammatory memory (HSC-iM).
“A key next step is to determine the mechanisms for HSC-iM formation following recovery from inflammatory stress and whether we can prevent or reverse the HSC-iM state,” Xie explained. “I aim to show empirically that diet alterations can directly mitigate inflammation-induced molecular changes in human HSCs.”
Yash Chhabra, PhD, of Fox Chase Cancer Center, was motivated to study how both age- and sex-dependent changes can impact cancer progression for a different reason—the lack of representation of elderly patients in melanoma clinical trials. Given that the aging population is expected to double by 2050, Chhabra recognized this as a critical gap. So he turned to emerging technologies and multiomics approaches—like many of his fellow NextGen Stars—to investigate the interconnections between age, sex, and the tumor microenvironment that are shaping cancer development and treatment response.
“By integrating genetic, epigenetic, metabolic, and immunological influences, we can move beyond the ‘one-size-fits-all’ approach, refining diagnostic and therapeutic strategies to match the unique biological and environmental context of each patient,” Chhabra said. “This shift will not only improve treatment efficacy and patient outcomes but also enhance our ability to predict therapy responses, reduce adverse effects, and bridge existing disparities in cancer care.”
Learning From Resistance
Epigenetics, the study of how genes are controlled, is at the heart of the research being conducted by Adam Durbin, MD, PhD, of St. Jude Children’s Research Hospital. Epigenetic changes can turn genes “on” or “off,” and Durbin and his colleagues have developed a system that allows them to monitor the epigenetic state of a cancer cell in real time. The goal is to determine how epigenetic therapy can be used to reprogram cells to boost the effectiveness of therapy, for example, by making tumor cells express genes that make them more sensitive to chemotherapy.
“There’s data from many different groups that show a lot of heterogeneity across tumor types and that heterogeneity is not always mediated by mutations,” Durbin explained. “There seems to be cells that express different transcriptomes and have different malignant properties, including resistance to chemotherapy, despite having the same genetic mutations. We’ve been focusing on finding ways to control the malignant properties of neuroblastoma, but I think these principles may apply broadly, and I hope there’s interest from the research community to explore these same principles in many other types of cancer.”
That doesn’t mean that genetic mutations don’t also contribute to tumor cells’ responsiveness to therapies, and Di Zhao, PhD, of The University of Texas MD Anderson Cancer Center, is looking at how the cancer genome impacts the tumor immune microenvironment and what it means for the effectiveness of immunotherapies. By combining state-of-the-art mouse model systems and single-cell multiomics, she is trying to identify the genetic determinants behind the development of prostate cancer.
“In five years, I would like to see prostate cancer research make significant strides in the identification of robust biomarkers for early detection and treatment response prediction,” Zhao said. “I also hope this research leads to the refining of personalized and combinatorial therapies to stop cancer before it becomes aggressive and the deepening of our understanding of the tumor microenvironment to fully unleash the power of checkpoint immunotherapy in advanced prostate cancer.”
Zuzana Keckesova, PhD, on the other hand, is asking a completely different question about resistance in relation to cancer: What can we learn from the tissues where cancer rarely develops? Keckesova, who is at the Institute of Organic Chemistry and Biochemistry of the CAS in the Czech Republic, pointed to heart cancer or adult skeletal muscle cancer as examples. By working with cancers like these—which she calls cancer-resistant tissues—she has been able to identify novel tumor suppressive pathways that may be a key to identifying cancer treatments.
“I hope this research can lead to the identification of new sensitivities of cancer cells and to new cancer targets,” Keckesova explained.
Looking for New Ways to Target Cancer
Another strategy for overcoming resistance to some therapies is to identify new ways to boost antitumor immunity. For Karen Dixon, PhD, of the University of Basel in Switzerland, that has involved a fascination with dark kinases in the phosphoinositide (PI) pathway, which have been understudied or poorly understood. Along with her colleagues, they have found that PI5P4K𝛾 plays a role in regulating antitumor immunity and that by targeting PI5P4K𝛾 it may be possible to both enhance the immune response in melanoma and reduce tumor growth.
“Numerous molecules in the PI pathway have been implicated in various immunological and neurological disorders, along with many solid and hematological malignancies. They have proven to be highly targetable with small-molecule inhibitors, but this does not address the need to target the largely overlooked members of this pathway which have enormously important housekeeping and signaling functions, yet possess low to no catalytic activity,” Dixon explained. “Moving forward in the next five to 10 years, targeted protein degradation may significantly expand the druggable space in the PI pathway far beyond small-molecule inhibitors.”
Other researchers, like Edmond Chan, MD, are investigating more well-known targets that have been studied for years but have yet to result in any approved therapies. Chan, of Columbia University, said that advances in high-throughput ’omic technologies and modeling approaches are helping researchers learn more about these potential targets, such as the Werner syndrome protein (WRN). Previously, Chan and his colleagues discovered the WRN RecQ helicase as a synthetic lethal target for cancers with microsatellite instability-high (MSI-H), which has led to ongoing clinical trials to evaluate WRN inhibitors. More recently, they have identified another synthetic lethal target for MSI-H cancers as well as cancers harboring biallelic deletions in chromosome 9p21.3—pelota ribosome rescue factor.
“I believe that fundamental understanding of drug mechanisms is critical for optimal implementation of novel therapeutics, and I hope that the targets that we have and will identify spark drug discovery efforts and clinical trials,” Chan said. “We will continue to interrogate the molecular underpinnings of important phenomena in cancer, but I also believe that it is equally important to be an usher to the next generation of cancer scientists. I certainly benefited from the amazing mentors who have supported and guided me along the way. I hope to pay it forward as a mentor myself.”
Hear about all of the NextGen Stars exciting discoveries at the AACR Annual Meeting 2025, and check out the Online Itinerary Planner for the latest information on session times and locations.
