Combination of PARP Inhibitor and P13K Inhibitor Shows Promise 2017-04-04T18:26:26+00:00

Combination of PARP Inhibitor and P13K Inhibitor Shows Promise

Publication date: November, 2012

For the treatment of triple-negative breast cancer, the combination of two investigational drugs-a PARP inhibitor and a P13K inhibitor-may be more effective than either drug alone. This drug combination is just beginning to be studied in humans, but the results of two laboratory studies were recently reported in Cancer Discovery.

The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Drugs that inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy. Because many triple-negative breast cancers are thought to have defects in DNA repair, researchers have hypothesized that triple-negative breast cancers may be particularly vulnerable to PARP inhibition. The benefits seen in studies thus far, however, have been somewhat limited.

PI3-kinase (P13K) plays a role in a signaling pathway that is often activated inappropriately in triple-negative breast cancer.

The two studies published in Cancer Discovery both evaluated the combination of a PARP inhibitor and a P13K inhibitor. Neither of the studies involved humans-one of the studies evaluated triple-negative breast cancer cells in the laboratory and the other evaluated BRCA1-positive breast tumors in mice-but both studies found promising results:

  • The P13K inhibitor made cancer cells more sensitive to the effects of the PARP inhibitor.
  • In mice, the treatment combination significantly delayed cancer progression.

The results suggest that a combination of two drugs-one that inhibits PARP and one that inhibits P13K-may be a promising approach to the treatment of triple-negative breast cancer. A Phase I clinical trial to evaluate this treatment combination in humans is already underway. The study is enrolling patients with triple-negative breast cancer or ovarian cancer.

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Ibrahim YH, Garcia-Garcia C, Serra V et al. P13K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient triple-negative breast cancer to PARP inhibition.
Cancer Discovery. 2012;2:1036-1047.
Juvekar A, Burga LN, Hu H et al. Combining a P13K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer. Cancer Discovery. 2012;2:1048-1063.[ Full text available here ] [ Full text available here ]

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