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.