Have You Seen This?: PARPi Beyond BRCA

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Holly Magliochetti

Genetics Institute of America

Genetics Institute of America (GIA) is a national laboratory dedicated to heightening the awareness of early intervention and genetic screening to promote the longevity and quality of life outcomes.  


Have You Seen This? 


DELRAY BEACH, FL  – Since 2014, there has been a well-established connection between the use of PARP inhibitors in BRCA-positive breast and ovarian cancer patients with an improved overall survival rate. “A mounting body of evidence now indicates that PARP inhibitors (PARPi) have the potential to be used as a foundation for both monotherapy and combination strategies across a wide spectrum of molecular backgrounds and tumor types,” not just with BRCA-positive patients.1

PARPi are now being investigated in many ongoing clinical trials targeting a wide range of biomarkers, including ATM, ATR, CHK1, CHK2, TP53, and RB1, in a variety of cancers. Researchers are attempting to extend the clinical benefits of PARPi by administering them earlier in treatment, seeking chemoprevention strategies and testing combination treatments.1 “If we also take into account the potential to reverse acquired PARP inhibitor monotherapy resistance using PARP inhibitor-DDR [DNA Damage Response] inhibitor combinations…while broadening the patient populations beyond what is obtainable through monotherapy via combinations with other targeted agents such as inhibitors of VEGFR, PI3K pathways, other oncogenic drivers such as AR [androgen receptor] and immunotherapy, as well as other DDR-targeted agents, it is clear that PARP inhibitor benefits have the potential to go well beyond the initial impressive advances experienced in recent years.”1

DDR-targeted therapies have revolutionized treatment for breast and ovarian cancer patients, with the help of germline variant predisposition data. “DDR deficiencies are common in cancer and indeed have been postulated to be a necessary component of tumorigenesis, but they also represent an Achilles’ heel that can now be targeted.”1 Maximizing the number of cancer patients who could benefit from PARPi use could truly change oncology towards individualized treatment, increased patient satisfaction and greater overall survival.

  1. Pilié PG, Gay CM, Byers LA, O’Connor MJ, Yap TA. PARP Inhibitors: Extending Benefit Beyond BRCA-Mutant Cancers. Clin Cancer Res. 2019;25(13):3759-3771. doi:10.1158/1078-0432.CCR-18-0968
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