Small cell lung cancer (SCLC), characterized by early metastasis, relapse, relapse and resistance and poor prognosis, still faces difficulties in treatment. Recently, Immunotherapy is a novel treatment for SCLC, researchers are also eager to achieve a breakthrough in targeted treatment of SCLC. Genomic instability of SCLC and sensitivity to cytotoxic chemotherapy, therefore, poly ADP-ribose polymerase (PARP) inhibitors targeting DNA repair related pathways have become a hotspot in the research of SCLC targeted therapy. Studies on PARP inhibitors in SCLC have been conducted in combination with other therapeutic strategies, including the treatment of recurrent SCLC and first-line treatment,as well as maintenance treatment after induction. These studies also explored the predictive markers of PARP inhibitors in SCLC. Although the current results of PARP inhibitors in SCLC are limited, and the predictive markers are also inconsistent, we also see that PARP inhibitors could be a breakthroughfor precision medicine of SCLC. .
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.102.19 | DOI Listing |
Investig Clin Urol
January 2025
Basic-Clinic Convergence Research Institute, University of Ulsan, Ulsan, Korea.
Purpose: Developmentally regulated GTP-binding protein 2 (DRG2) regulates microtubule dynamics and G2/M arrest during docetaxel treatment. Poly ADP-ribose polymerase (PARP) acts as an important repair system for DNA damage caused by docetaxel treatment. This study investigated whether DRG2 expression affects response to PARP inhibitors (olaparib) using prostate cancer cell lines PC3, DU145, LNCaP-FGC, and LNCaP-LN3.
View Article and Find Full Text PDFCA Cancer J Clin
January 2025
Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.
Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Selective poly(ADP-ribose) polymerase 1 (PARP1) inhibitors not only exhibit antitumor efficacy but also offer the potential to mitigate the toxicities typically associated with broader PARP inhibition. In this study, we designed and synthesized a series of small molecules targeting highly selective PARP1 inhibitors. Among these, demonstrated excellent selectivity to PARP1 along with the capability to effectively cross the blood-brain barrier (BBB).
View Article and Find Full Text PDFCancer Res Treat
January 2025
Cancer Research Institute, Seoul National University, Seoul, Korea.
Purpose: This study focused on combining irinotecan with Poly (ADP-ribose) polymerase (PARP) inhibitors to explore the potential for novel combination therapeutics in small cell lung cancer (SCLC).
Materials And Methods: We selected 10 different SCLC cell lines with diverse mutational backgrounds in DNA damage response (DDR) pathway genes to evaluate the efficacy of the combination of three PARP inhibitors and irinotecan. After the cells were exposed to the drugs for seven days, cell viability was measured, and a combination index was calculated.
Eur J Med Chem
January 2025
School of Medical and Information Engineering, School of Pharmacy, Gannan Medical University, Ganzhou, 341000, PR China; Jiangxi Provincial Key Laboratory of Tissue Engineering, Gannan Medical University, Ganzhou, 341000, PR China. Electronic address:
Epigenetic dysregulation plays a pivotal role in the initiation and progression of various cancers, influencing critical processes such as tumor growth, invasion, migration, survival, apoptosis, and angiogenesis. Consequently, targeting epigenetic pathways has emerged as a promising strategy for anticancer drug discovery in recent years. However, the clinical efficacy of epigenetic inhibitors, such as HDAC inhibitors, has been limited, often accompanied by resistance.
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