PARP inhibitor
PARP inhibitor
PARP inhibitors are a class of pharmacological inhibitors of the enzyme Poly ADP ribose polymerase (PARP). They are primarily used in the treatment of cancer, particularly ovarian cancer, breast cancer, prostate cancer, and pancreatic cancer. PARP inhibitors exploit the concept of synthetic lethality to target cancer cells with specific genetic deficiencies, such as BRCA1 or BRCA2 mutations.
Mechanism of Action[edit | edit source]
PARP inhibitors work by inhibiting the PARP enzyme, which plays a critical role in the repair of single-strand DNA breaks through the base excision repair pathway. When PARP is inhibited, single-strand breaks accumulate and eventually lead to double-strand breaks during DNA replication. In normal cells, these double-strand breaks can be repaired by the homologous recombination repair pathway. However, in cancer cells with BRCA1 or BRCA2 mutations, this repair pathway is defective, leading to cell death.
Clinical Applications[edit | edit source]
PARP inhibitors have shown significant efficacy in treating cancers with BRCA1 or BRCA2 mutations. They are also being investigated for use in other cancers with deficiencies in DNA repair mechanisms. Some of the approved PARP inhibitors include:
Side Effects[edit | edit source]
Common side effects of PARP inhibitors include nausea, fatigue, anemia, and thrombocytopenia. More severe side effects can include myelodysplastic syndrome and acute myeloid leukemia.
Research and Development[edit | edit source]
Ongoing research is focused on expanding the use of PARP inhibitors to other types of cancer and understanding the mechanisms of resistance that some tumors develop. Combination therapies with other agents, such as immune checkpoint inhibitors, are also being explored.
See Also[edit | edit source]
References[edit | edit source]
External Links[edit | edit source]
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