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Open AccessArticle

Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status

1
Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA
2
David Geffen UCLA School of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095, USA
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(4), 940; https://doi.org/10.3390/jcm9040940
Received: 7 March 2020 / Revised: 26 March 2020 / Accepted: 27 March 2020 / Published: 30 March 2020
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Breast Cancer)
Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven to be beneficial to patients with metastatic breast cancer with BRCA1/2 (BReast CAncer type 1 and type 2 genes) mutations. However, certain PARPi in pre-clinical studies have been shown to inhibit cell growth and promote the death of breast cancer cells lacking mutations in BRCA1/2. Here, we examined the inhibitory potency of 13 different PARPi in 12 breast cancer cell lines with and without BRCA-mutations using cell viability assays. The results showed that 5 of the 8 triple-negative breast cancer (TNBC) cell lines were susceptible to PARPi regardless of the BRCA-status. The estrogen receptor (ER) negative/ human epidermal growth factor receptor 2 (HER2) positive (ER-/HER2+) cells, SKBR3 and JIMT1, showed high sensitivity to Talazoparib. Especially JIMT1, which is known to be resistant to trastuzumab, was responsive to Talazoparib at 0.002 µM. Niraparib, Olaparib, and Rucaparib also demonstrated effective inhibitory potency in both advanced TNBC and ER-/HER2+ cells with and without BRCA-mutations. In contrast, a BRCA-mutant TNBC line, HCC1937, was less sensitive to Talazoparib, Niraparib, Rucaparib, and not responsive to Olaparib. Other PARPi such as UPF1069, NU1025, AZD2461, and PJ34HCl also showed potent inhibitory activity in specific breast cancer cells. Our data suggest that the benefit of PARPi therapy in breast cancer is beyond the BRCA-mutations, and equally effective on metastatic TNBC and ER-/HER2+ breast cancers. View Full-Text
Keywords: PARP inhibitors; Triple-negative breast cancer; BRCA1/2 mutations; HER2-positive breast cancer PARP inhibitors; Triple-negative breast cancer; BRCA1/2 mutations; HER2-positive breast cancer
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Keung, M.Y.; Wu, Y.; Badar, F.; Vadgama, J.V. Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status. J. Clin. Med. 2020, 9, 940.

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