Breast cancer is a collection of diseases with heterogeneous molecular features and clinical behaviors. Among these disease subtypes, triple-negative breast cancer (TNBC) is the most aggressive, and the molecular determinants of TNBC are poorly understood. Recently, our group has discovered new tumor suppressor networks that are disrupted in more than 70 percent of TNBCs (Sun et al., Cell 2011; Nair et al., Nature Medicine 2018), with the tyrosine phosphatase PTPN12 acting as a core component of this network.
Importantly, disruption of this tumor suppressor network leads to the concerted hyper-activation of a class of receptor tyrosine kinases that work together to drive TNBC and probably other cancers. Importantly, we have shown that pharmacologic inhibition of these collaborating kinases leads to tumor regression of primary TNBCs in vivo.
We are currently dissecting the mechanism(s) by which these signaling pathways cooperate, and translating these discoveries into new clinical trials for TNBC patients at Baylor College of Medicine.
