The Mark Foundation Center for Lineage Plasticity is working to understand and combat the progression of deadly cancers like bladder and esophageal cancer. Led by co-principal investigators Cory Abate-Shen, PhD, Anil Rustgi, MD, and Michael Shen, PhD, from Columbia University’s Herbert Irving Comprehensive Cancer Center, and David Solit, MD from Memorial Sloan Kettering Cancer Center, this collaborative initiative challenges the conventional assumption that these cancers are mechanistically distinct.
The Center’s origins lie in a previous Endeavor Award project that revealed the critical role of lineage plasticity – a cancer cell’s ability to change its identity – in bladder cancer progression. This initial work yielded valuable resources, including genetically engineered mouse models and a comprehensive biobank of longitudinal human bladder cancer samples. Recognizing the broader implications of these findings, the team expanded its focus to include esophageal cancer.
This Center, supported by The Mark Foundation and Torrey Coast Foundation, will delve into the shared mechanisms driving the progression of bladder and esophageal cancers. By investigating the epigenetic regulation of lineage plasticity, particularly focusing on key enzymes like lysine methyltransferase 2D (KMT2D) and lysine-specific demethylase 1A (KDM1A), researchers aim to pinpoint new therapeutic targets. This integrated effort, involving collaborators from Columbia University Irving Medical Center, the Chan Zuckerberg Biohub New York, Memorial Sloan Kettering Cancer Center, Perlmutter Cancer Center at New York University Langone Health, and the Wellcome Sanger Institute, seeks to develop strategies to reverse or block plasticity, ultimately hindering cancer progression and improving patient outcomes across a broader range of cancers.