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olaparib + gemcitabine
- Development stage
- Phase 1
- Lead developer
- AstraZeneca
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
Olaparib + gemcitabine is a combination of two anticancer agents: olaparib, an oral small-molecule inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes (PARP-1 and PARP-2), and gemcitabine, an intravenous nucleoside analog that inhibits DNA synthesis. Olaparib exploits synthetic lethality in cancers with homologous recombination repair defects, such as those harboring BRCA mutations, potentiating the effects of DNA-damaging chemotherapy. Gemcitabine is incorporated into DNA and inhibits DNA polymerase, leading to apoptosis of tumor cells. The combination has been studied in patients with advanced solid tumors, including pancreatic and other cancers, to determine safety, tolerability, and optimal dosing schedules. While activity has been observed, the combination is associated with frequent dose-limiting hematologic toxicities, particularly myelosuppression, requiring intermittent dosing strategies for tolerability[1][2].
- Other names
- olaparib + gemcitabine
02
Targets
DNA polymerase familyPARP1 (Poly (adp-ribose) polymerase 1)PARP2 (Poly (adp-ribose) polymerase 2)PARP3 (Poly(adp-ribose) polymerase 3)Pol II (RNA polymerase II elongation factors)
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