Weill Cornell Medicine
We develop computational and experimental tools to study cancer as a complex evolutionary process. Our research is geared towards discovering the basic principles that allow malignant cells to continuously evolve, diversify and overcome therapy. The lab’s goal is to chart a roadmap of the basic dimensions that determine the course of cancer evolution, in order to devise therapies that directly anticipate and address it.
Dan Landau, MD, PhD, is a physician-scientist who has pioneered the study of cancer evolution as a central obstacle on the path to curative therapy. His work has delineated the evolutionary course that allows cancer cells to rescind the multicellular contract, diversify and become resistant to therapy. Dr. Landau completed undergraduate and medical school degrees at Tel Aviv University, and PhD training at Paris Diderot University. His post-graduate training included internal medicine, hematology and medical oncology training at Yale University. He also completed a post-doctoral research fellowship at the Dana Farber Cancer Institute and the Broad Institute of Harvard and MIT. In 2016, he was jointly appointed as an assistant professor of medicine and a member of the Institute of Computational Biomedicine at Weill Cornell Medicine, as well as a core member of the New York Genome Center. He cares for bone marrow transplant patients at the New York Presbyterian hospital. His work was recognized with awards from Burroughs Wellcome Fund, NIH Big Data to Knowledge initiative, Stand Up to Cancer, Leukemia & Lymphoma Society, American Society of Clinical Investigation, Sydney Kimmel Foundation, and American Society of Hematology.
Shapeshifters in Cancers – Defining Epidrivers of Cancer Evolution in Response to Targeted Therapy
Targeted cancer therapies lead to remarkable disease remissions across a range of human cancers. Unfortunately, the remissions are often short-lived as the cancer adapts to the therapeutic intervention through an intensive evolutionary process. Ongoing changes in the growing cancer cell population lead to marked heterogeneity, challenging our therapies to overcome not a single disease entity, but rather thousands of variants of the disease within each patient. Thus, the ability of cancer to diversify and evolve poses a central obstacle to cancer cure today. Most of the studies to date have focused on DNA mutations as a major driving force in cancer diversity and evolution to therapeutic resistance. These studies have catalyzed second and third generation targeted agents designed to overcome the DNA mutations that provide resistance. However, we – and others – have shown that cancer evolution is also fueled by heritable changes that are not genetically encoded (‘epigenetic’). We currently lack a framework to identify these changes for therapeutic targeting.
“We are grateful to join the unique community of the Pershing Square Sohn Cancer Research Alliance. This support will enable us to tackle the major challenge of non-genetic dimensions of cancer evolution.”
Our proposal seeks to tackle these non-genetic mechanisms driving cancer evolution, which remains a major, underexplored, emerging theme across the field of oncology. To do so, we have developed unique tools to define genetic and non-genetic changes at the level of a single cancer cell. Using these tools to generate experimental models and measurements in patient leukemia samples, our studies will enable precision customization of anti-cancer therapy to prevent non-genetic evolution to treatment resistance.
“Our path to innovation is anchored in the close integration across disciplines; combining computational advances, molecular biology technology development and novel conceptual frameworks in cancer biology.”