Understanding resistance to therapy in cancer

A mechanism that may account for the resistance of certain breast tumors to therapy is published online this week in Nature Medicine. These findings could have potential clinical use as a solution to overcome drug resistance. Trastuzumab (Herceptin) is an antibody used for certain women with breast cancer, but not every patient who should respond to it exhibits a response. The mechanisms that account for this resistance to therapy are unclear and often very diverse, which makes it difficult to identify and target them. Dihua Yu and her colleagues have discovered that the enzyme tyrosine kinase c-SRC is a key modulator of multiple trastuzumab resistance pathways. c-SRC is commonly activated in cancer cells with different intrinsic and acquired resistance-driving mechanisms, and the increased c-SRC activation conferred trastuzumab resistance in breast cancer cells that would otherwise respond to the antibody. Inhibiting c-SRC in combination with trastuzumab turned trastuzumab-resistant tumors into trastuzumab-sensitive tumors, underscoring the potential clinical use of this strategy to overcome multiple modes of trastuzumab resistance.