can we figure out how non-genetic differences between cancer cells allow therapeutic resistance?

Anti-cancer therapies have generated significant attention and enthusiasm regarding their potential in treating cancer. However, these drugs often cannot kill every tumor cell, leaving behind rare surviving cells that trigger relapse in patients. Although much effort has gone into probing the genetic determinants of therapeutic resistance, Dr. Goyal and others have recently shown that non-genetic variability or “plasticity” in cancer cells plays a larger role than previously appreciated in driving therapeutic resistance. Still, little is known about the mechanistic origins and consequences of non-genetic plasticity on the fate of cancer cells exposed to anti-cancer drugs. For his CRF Young Investigator Award, Dr. Goyal will pursue a number of transdisciplinary approaches to address these gaps in our cancer knowledge.

Dr. Goyal plans to develop novel experimental and computational frameworks combining sequencing and imaging to track plasticity and fate choices in single cancer cells. Leveraging this framework, Dr. Goyal will reveal the unifying pan-cancer mechanisms that may allow particular rare cells to escape therapy. Such rich mechanistic information will present novel therapeutic opportunities, enabling Dr. Goyal to screen for modulators capable of inducing or eliminating plasticity causing resistance. His multiscale approach—integrating ideas from engineering, synthetic biology, cancer biology, mathematics, and computer science—promises to provide novel conceptual and technical frameworks to control single-cell heterogeneity in cancer.