“Rewiring” Cells to Treat Triple Negative Breast Cancer

Breast cancer cells can be “rewired” to make them more sensitive to chemotherapy, according to a new study published in the journal Cell. Rather than giving targeted therapy and chemotherapy simultaneously, researchers at the Massachusetts Institute of Technology (MIT) pretreated the cancer cells with targeted therapy, making them more susceptible to DNA-damaging chemotherapy.

Dr. Michael Yaffe and colleagues analyzed how normal and oncogenic signaling can be rewired in cells from women with triple-negative breast cancer. In their sequential approach of administering erlotinib (Tarceva), which blocks the activity of epidermal growth factor receptor (EGFR), followed by the chemotherapy drug, doxorubicin at least twenty-four hours later, they found that about 40% of the cell lines responded to doxorubicin. Moreover, seventy-two hours after administration of the two drugs, none of the cells that had responded were still alive. “This process converts these cells to a less tumorigenic state that is more susceptible to DNA damage-induced cell death by reactivation of an extrinsic apoptotic pathway whose function is suppressed in the oncogene-addicted state,” explain the scientists. The researchers are currently planning a clinical trial.

According to Dr. Dan Gallahan of NCI’s Division of Cancer Biology, “We know that cancer cells evolve and develop resistance to therapies. This study illustrates how new information about the signaling pathways in cancer cells that emerge from a systems-biology approach can be used to manipulate cancer.”


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