Research ArticleCancer

Androgen receptor inhibitor–induced “BRCAness” and PARP inhibition are synthetically lethal for castration-resistant prostate cancer

See allHide authors and affiliations

Sci. Signal.  23 May 2017:
Vol. 10, Issue 480, eaam7479
DOI: 10.1126/scisignal.aam7479

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Engineering BRCAness and chemotherapeutic sensitivity

BRCA mutations impair a double-strand break DNA repair pathway that forces cells to use a PARP-dependent repair pathway. PARP inhibitors are selectively toxic to breast cancers with BRCA mutations, spurring the search for other tumors or ways in which to apply such exquisitely tumor-targeted therapy. Few other tumors have BRCA mutations as commonly as do breast tumors. However, Li et al. found that a common therapy for prostate cancer patients created a BRCA-deficient state that sensitized tumor cells to PARP inhibitors and leveraged this finding into a potential treatment strategy. Noting that the androgen receptor inhibitor enzalutamide decreased the expression of BRCA1 in prostate cancer cells, the authors treated a mouse model of prostate cancer first with enzalutamide and then with the PARP inhibitor olaparib. Sequential treatment of enzalutamide and olaparib suppressed tumor growth in these mice better than either drug by itself or when both drugs were administered at the same time. The results suggest that “BRCAness” could be therapeutically induced to provide more treatment options not only for prostate cancer patients but also for patients with other types of cancers lacking BRCA mutations.