Bladder cancer and esophageal cancer are both deadly and difficult to treat — but to date, these diseases have been treated as mechanistically distinct.
The newly announced Mark Foundation Center for Lineage Plasticity is challenging that status quo with a multi-cancer approach that could unlock new treatments for these and other tumor types. The Center, awarded $10 million in funding over five years by The Mark Foundation and Torrey Coast Foundation, also demonstrates the momentum that can arise when talented researchers from across disciplines are given the support and resources to pursue their most innovative ideas. 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 will lead the project as a collaborative effort.
Building on Success
The origins of the Mark Foundation Center for Lineage Plasticity lie in an Endeavor Award granted in 2021 to a team of researchers including Abate-Shen, Shen, and Solit.
The Endeavor project yielded critical insights into the role of lineage plasticity – a cell’s ability to change its identity – during bladder cancer progression. Additionally, the team developed valuable resources including genetically engineered mouse models and an expanding biobank of longitudinal human bladder cancer samples.
While these findings have significantly advanced our understanding of bladder cancer, Abate-Shen and her collaborators recognized that their findings on lineage plasticity had implications that spanned beyond bladder cancer.
To expand the work, Abate-Shen, Shen, and Solit invited Rustgi to join their application to launch a Mark Foundation Center aimed at exploring lineage plasticity across multiple cancer types, including esophageal cancer, one of Rustgi’s areas of research focus.
A Multi-Cancer Approach
The new Center will employ a multi-cancer approach using bladder and esophageal cancers as models. This approach is based on findings that emerged from the Endeavor project that these distinct cancer types show unexpected similarities in the pathways that drive their progression.
To unravel these shared mechanisms, the Center’s powerhouse team — with co-investigators and collaborators drawn 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 — will investigate the epigenetic regulation of lineage plasticity, with a particular focus on two key enzymes, lysine methyltransferase 2D (KMT2D) and lysine-specific demethylase 1A (KDM1A), which both play a critical role in controlling cancer cell gene expression linked to tumor plasticity and progression. By understanding how these proteins and other factors regulate changes to cancer cells, the researchers aim to pinpoint new therapeutic targets and develop strategies to reverse or block plasticity, ultimately hindering cancer progression.
Fueling Transformative Research
By targeting the fundamental processes driving tumor plasticity, this research holds immense promise for developing new therapeutic strategies. The Center’s integrated approach, spanning basic research to clinical trials, is poised to transform the treatment landscape for bladder cancer, esophageal cancer, and potentially a broader range of cancers for which lineage plasticity facilitates disease progression.
It also demonstrates the value of fostering interdisciplinary partnerships and giving scientists the resources and flexibility to pursue their most innovative ideas and approaches.
“As the Center for Lineage Plasticity shows us, targeted research investments can lead to significant breakthroughs,” said Ryan Schoenfeld, PhD, CEO of The Mark Foundation. “By empowering investigators like Cory and her collaborators to make fundamental mechanistic discoveries and translate them into new therapeutic options, we can deliver new treatments to patients faster.”
Learn more about Mark Foundation Centers.