Recent advances in cancer therapy using PARP inhibitors.

Kaur, Simran Deep, Chellappan, Dinesh Kumar, Aljabali, Alaa A , Tambuwala, Murtaza, Dua, Kamal and Kapoor, Deepak N (2022) Recent advances in cancer therapy using PARP inhibitors. Medical Oncology, 39 (12). p. 241. ISSN 1357-0560

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Recent advances in cancer therapy using PARP inhibitors.
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When DNA repair is inadequate it increases the chances of the genome becoming unstable and it undergoes a malignant mutation. The deficiency of DNA repair PARP proteins may be leveraged for cancer therapy by increasing genomic instability and causing massive DNA damage in cancer cells. DNA repair components are under increased demand in cancer cells because of the continuous replication of DNA. The oncogenic loss of BRCA and an inefficient DNA repair led to cancer cells being dependent on particular DNA repair pathways, like the Poly (ADP-ribose) polymerase pathway. Breast cancer gene 1 and 2 plays a crucial role in DNA repair and genome integrity explaining how BRCA1 and BRCA2 mutations raise the menace of cancer. PARP inhibitors inhibit the base exclusion repair pathway, resulting in the buildup of unrepaired single strand breaks, which cause inflated replication forks in the S phase and subsequently the development of damaging double stranded breaks. Cells having BRCA mutations are unable to repair DNA breaks, leading to apoptosis and eventually death of cancer cells. Numerous indicators, such as a lack of homologous recombination and a high degree of replication pressure, indicate that this therapy will be very effective. Combining PARP inhibitors with chemotherapy, an immune checkpoint inhibitor, and a targeted drug is an effective strategy for combating PARP inhibitors resistance. Several PARP-based combination approaches are in preclinical and clinical development. Various clinical trials are successfully completed and some are undergoing to evaluate the efficacy of these molecules. This review will describe the current views and clinical updates on PARP inhibitors.

Keywords:Breast cancer gene (BRCA), Double strand breaks (DSBs), HER2 receptor, PARP inhibitors, PDL1 inhibitors, Single strand breaks (SSBs)
Subjects:A Medicine and Dentistry > A300 Clinical Medicine
Divisions:COLLEGE OF HEALTH AND SCIENCE > Lincoln Medical School - Universities of Nottingham and Lincoln
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ID Code:51980
Deposited On:14 Nov 2022 14:52

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