While initially highly successful, targeted therapies eventually fail as populations of tumor cells evolve mechanisms of resistance, leading to resumption of tumor growth. Historically, cell-intrinsic mutational changes have been the major focus of experimental and clinical studies to decipher origins of therapy resistance. While the importance of these mutational changes is undeniable, a growing body of evidence suggests that non-cell autonomous interactions between sub-populations of tumor cells, as well as with non-tumor cells within tumor microenvironment, might have a profound impact on both short term sensitivity of cancer cells to therapies, as well as on the evolutionary dynamics of emergent resistance. In contrast to well established tools to interrogate the functional impact of cell-intrinsic mutational changes, methodologies to understand non-cell autonomous interactions are largely lacking... This manuscript serves as a technical report and will be followed up with a research paper in a different journal. READ ARTICLE
BioRxiv DOI:10.1101/2020.11.30.404350
Authors: Ranjini Bhattacharya, Robert Vander Velde, Viktoriya Marusyk, Bina Desai, Artem Kaznatcheev, Andriy Marusyk, David Basanta