Evolving Our Understanding of Cancer’s Evolution, Progression, and Persistence

Cancers constantly evolve. It begins with a mutation that leads a normal cell to become a cancer cell and from there the cancer cell multiplies and often spreads to other parts of the body and adapts along the way to ensure survival. Cancer evolves to find ways to resist treatment and even return after seemingly being eliminated. But advances in spatial biology and computational modeling are allowing researchers to discover new insights about the evolution of cancer, according to Laura M. Heiser, PhD, who is the chair of the American Association for Cancer Research (AACR) Cancer Evolution Working Group (CEWG). This working group was established in 2021 with the mission to foster a deeper understanding of cancer evolution that can guide improvements in early detection, diagnosis, and treatment.

“The CEWG has been quite active in building a community of researchers to promote the integration of evolutionary principles of cancer into all areas of cancer research, and bringing those ideas to the broader AACR community,” explained Heiser, who is associate professor and vice chair in the Department of Biomedical Engineering at Oregon Health & Science University.

That is why the CEWG proposed the AACR Special Conference in Cancer Research—Cancer Evolution: The Dynamics of Progression and Persistence. To be held December 4-6, 2025, at the Clyde Hotel in Albuquerque, New Mexico, this meeting is chaired by Mariam Jamal-Hanjani, MD, PhD, clinician scientist and group leader at the University College London (UCL) Cancer Institute in the United Kingdom; Kenneth J. Pienta, MD, Donald S. Coffey Professor of Urology and a professor of oncology at the Johns Hopkins School of Medicine; and Mara H. Sherman, PhD, associate member of cancer biology and genetics at Memorial Sloan Kettering Cancer Center.

The conference will explore the evolutionary principles of cancer from its initiation to relapse. The program features sessions exploring evolutionary biology, tumor evolution, resistance mechanisms, metastasis, tumor co-evolution, the tumor microenvironment, advances in computational approaches, potential clinical applications, and more.  

Cancer Research Catalyst spoke with Heiser and Sherman about the latest advancements in the understanding of cancer evolution and what to expect at the upcoming conference.

What made this the right time for a conference focused on cancer evolution?

Mara Sherman: Newer clinical trial designs are increasingly enabling an understanding of how tumors change over time and evolve during treatment, allowing us to understand the dynamics of cancer progression and therapy resistance in a totally new light. In addition, elegant preclinical modeling and careful analyses of precancerous tissues in humans have opened up new lines of investigation into the early stages of cancer evolution, and potential new ways to screen for or prevent invasive cancer. The time is right to bring conceptually diverse researchers together and think of new ways to predict cancer behavior and intervene effectively.

Laura Heiser: There are now many exciting technological advancements allowing vast molecular measurements—including readouts that have traditionally been challenging—as well as new ways to consider the spatial biology of tumors. These capabilities are essential for understanding cancer onset and disease progression. Additionally, advancements in computational modeling—from mechanistic modeling to artificial intelligence (AI) approaches—are helping to inform the development and improvement of computational models. Those two approaches are closely intertwined and together can lead to new insights into mechanisms of cancer evolution. With this meeting, we aim to bring together the cancer research community to discuss these cutting-edge advances.

How is our understanding of cancer’s evolution evolving? How will these insights be included in the meeting?

Mara Sherman: Studies of cancer evolution are increasingly accounting for the so-called tumor macroenvironment, such as the mutual interactions between the evolving tumor and the ostensibly normal tissues of the host, which together influence tumor growth, metastatic spread, and diverse comorbidities that may impact patients’ ability to tolerate harsh therapies and, ultimately, their quality of life. These emerging concepts will be covered by several speakers at the conference.

Laura Heiser: The meeting’s eight Plenary Sessions will cover advancements in cancer evolution from across the spectrum. We will explore the very early stages of cancer, including how we can detect disease early and stratify individuals based on risk, as well as gain insights into the mechanisms that are driving disease. Presenters will also speak about the evolutionary mechanisms integral to therapeutic resistance.

Can you talk about the session you are chairing on the tumor microenvironment?

Mara Sherman: The tumor microenvironment session will cover diverse approaches—including computational approaches, patient-derived models, and preclinical studies—to understand how cancer cells and their surrounding stroma co-evolve during cancer progression and in response to therapy. We hope to motivate discussion of cellular hierarchies in the tumor microenvironment that may inform on cellular and molecular targets for new therapies. In addition to my talk, the session will include presentations from Elana J. Fertig, PhD, of the University of Maryland School of Medicine; Valerie M. Weaver, PhD, of the University of California, San Francisco (UCSF); and Ann-Marie Baker, PhD, of the Institute of Cancer Research in London, United Kingdom.

The CEWG chose “Tracing and Modeling Tumor Evolution” as a topic for the Plenary Session you will be chairing. Why did you want to focus on this subject?

Laura Heiser: Advances in experimental and computational approaches are already helping us to uncover evolutionary mechanisms driving progression and response to therapy. We will have Rohit Bose, MD, PhD, from UCSF, who is focused on prostate cancer and will be discussing how evolution of SETs, or Stochastically Emergent Tumors, could reveal potential vulnerabilities. Dian Yang, PhD, from Colombia, is using some exciting preclinical approaches to examine epigenetic changes associated with disease onset—starting from the first cell. Finally, Carlo Maley, PhD, from Arizona State University, has continued to push the envelope on computational approaches to cancer evolution. Together, the three speakers will address different angles of tumor evolution.

What do you hope attendees take away from the conference?

Mara Sherman: We hope attendees will head home with new ideas, collaborations, and questions to inform and shape their science. By bringing together an interdisciplinary community of researchers focused on diverse aspects of cancer evolution across tissue sites, we hope this conference will spark new ideas for everyone who joins us.

Laura Heiser: In this small meeting format there is a lot of time built in for informal discussion among attendees. I hope people leave with new connections to researchers studying different aspects of cancer evolution.

Register online to attend the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence.