Role of PARP inhibitors and cancers likely to respond.

• A. They are effective in all cancers regardless of HR status.
• B. They exploit synthetic lethality in HR-deficient tumors; effective in ovarian, fallopian tube, breast, pancreatic, and prostate cancers with BRCA/HRD
• C. They enhance DNA repair in BRCA wild-type tumors.
• D. They are only used in colon cancer.

Answer: (B)

The key idea is that PARP inhibitors work through synthetic lethality in tumors with homologous recombination deficiency. When BRCA1/2 or other HR repair pathways are impaired, inhibiting PARP traps cells in DNA damage that they can’t effectively repair, leading to cancer cell death while sparing normal cells with intact HR. This makes them especially effective in cancers commonly harboring BRCA mutations or HRD, such as ovarian, fallopian tube, breast, pancreatic, and prostate cancers. They aren’t universally effective in all cancers or in BRCA wild-type tumors with intact HR, and they don’t enhance DNA repair—in fact, they block repair. They’re not limited to colon cancer.