Systems-Level Analysis of EGFR Inhibition-DNA Damage Combination Treatment in Breast Cancer
Annual summary 1 Sep 2010-31 Aug 2011
MASSACHUSETTS INST OF TECH CAMBRIDGE
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Triple--negative breast cancer TNBC is a heterogeneous mix of cancers defined only by their lack of estrogen receptor expression, lack of progesterone receptor expression, and lack of amplification of the oncogene HER2. This lack of molecular etiology has limited our ability to rationally design therapies for TNBC, resulting in shorter relapse-free survival and a worse overall prognosis than other breast cancer patients. Here, we systematically screened various drug combinations, looking for those that were synergistic in killing triple--.negative breast cancer cells. Using targeted inhibition of oncogenic signaling pathways combined with chemotherapy, we report the surprising finding that time-staggered EGFR inhibition, but not simultaneous co-administration, can dramatically sensitize the apoptotic response of a subset of triple-negative cells to conventional DNA damaging agents. Only a subset of triple-negative cells 4 of 10 were sensitized by this combination, and importantly, these cells could not have been identified by their EGFR gene amplification.
- Anatomy and Physiology
- Medicine and Medical Research