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PI3-kinase and PARP inhibitor combo may offer new treatment option for triple-neg breast cancers
Date:11/12/2012

PHILADELPHIA The simultaneous inhibition of two separate and seemingly unrelated pathways could potentially provide an effective treatment for women with triple-negative breast cancer, according to results of two studies published in the November issue of Cancer Discovery, a journal of the American Association for Cancer Research.

Triple-negative breast cancers do not express three common targets of breast cancer treatments: the estrogen receptor, progesterone receptor and HER2/neu. As a result, women with triple-negative breast cancer have few treatment options. In early-phase clinical studies, those women with triple-negative breast cancer with BRCA1 gene mutations had some clinical benefit from treatments with poly-ADP-ribose-polymerase (PARP) inhibitors. However, the activity of the PARP inhibitors is short-lived.

"We are in desperate need of new therapies for triple-negative breast cancer, which is a type of breast cancer that is very aggressive and occurs mostly in young females," said Jos Baselga, M.D., Ph.D., chief of the division of hematology and oncology at Massachusetts General Hospital Cancer Center in Boston.

In their study, Baselga; Yasir Ibrahim, Ph.D., a postdoctoral fellow at Vall D'Hebron Institute of Oncology in Barcelona, Spain; and Maurizio Scaltriti, Ph.D., faculty assistant and lab coordinator at Massachusetts General Hospital Cancer Center, hypothesized that inhibiting PI3-kinase, a key component of a signaling pathway frequently activated inappropriately in triple-negative breast cancer, would replicate the conditions present in BRCA-mutated breast cancers, thereby increasing sensitivity to PARP inhibitors.

They found that if PI3-kinase function was blocked in a BRCA-proficient triple-negative breast cancer cell line, DNA damage would occur due to BRCA protein downregulation, and that this resulted in activation of PARP to repair the damage.

"In a way, with PI3-kinase inhibitors,
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Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

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