The cancer community has largely studied the effects of oncogenes and tumor suppressors and how they contribute to the “pro-tumorigenic” hallmarks of cancer cells. However, it’s also become clear that oncogenes themselves induce a variety of stresses in cancer cells that antagonize tumor growth and survival.
We are tackling several poorly understood questions related to oncogene-induced stresses:
• what are the molecular mechanisms by which prominent oncogenes (ex. Myc, Ras, etc.) induce these stresses?
• How do cancer cells tolerate these stresses?
• Are these stress support pathways different in normal and tumor cells?
We are integrating forward genetic technologies and proteogenomic profiling, we have nominated multiple cellular pathways that are required to tolerate prominent oncogenic aberrations (ex. Kessler et al, Science 2012; Hsu et al, Nature 2015). We are now extending these studies to elucidate the stress support pathways that enable cancer cells to tolerate other prominent drivers of breast cancer.