PARP inhibitors in small cell lung cancer: The underlying mechanisms and clinical implications

Wang, Xueting; Zeng, Xianhu; Li, Dan; Zhu, Chenhui; Guo, Xusheng; Feng, Lingxin; Yu, Zhigang

doi:10.1016/j.biopha.2022.113458

Cited by 5 publications

(2 citation statements)

References 146 publications

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“…Specifically, both pathways perform the same survival function to maintain cell viability, and aberrations in two or more genes that act as key regulatory points in both pathways lead to synthetic lethal interactions in tumors. Conversely, genetic anomalies in only one pathway can still sustain cell survival (Wang et al, 2022).…”

Section: Functional Pathway Levelmentioning

confidence: 99%

PARP inhibitors combined with radiotherapy: are we ready?

Sun,

Chu,

Song

et al. 2023

Front. Pharmacol.

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PARP was an enzyme found in the nucleus of eukaryotic cells that played a crucial role in repairing damaged DNA. Recently, PARP inhibitors have demonstrated great potential in cancer treatment. Thus, the FDA has approved several small-molecule PARP inhibitors for cancer maintenance therapy. The combination of PARP inhibitors and radiotherapy relies on synthetic lethality, taking advantage of the flaws in DNA repair pathways to target cancer cells specifically. Studies conducted prior to clinical trials have suggested that the combination of PARP inhibitors and radiotherapy can enhance the sensitivity of cancer cells to radiation, intensify DNA damage, and trigger cell death. Combining radiotherapy with PARP inhibitors in clinical trials has enhanced the response rate and progression-free survival of diverse cancer patients. The theoretical foundation of PARP inhibitors combined with radiotherapy is explained in detail in this article, and the latest advances in preclinical and clinical research on these inhibitors for tumor radiotherapy are summarized. The problems in the current field are recognized in our research and potential therapeutic applications for tumors are suggested. Nevertheless, certain obstacles need to be tackled when implementing PARP inhibitors and radiotherapies in clinical settings. Factors to consider when using the combination therapy are the most suitable schedule and amount of medication, identifying advantageous candidates, and the probable adverse effects linked with the combination. The combination of radiotherapy and PARP inhibitors can greatly enhance the effectiveness of cancer treatment.

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Section: Functional Pathway Levelmentioning

confidence: 99%

PARP inhibitors combined with radiotherapy: are we ready?

Sun,

Chu,

Song

et al. 2023

Front. Pharmacol.

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“…In 2018, talazoparib was approved for breast cancer treatment. 5 Figure 1 PARP inhibitor, mechanism of action. Chemotherapy, ionizing radiation can promote single-strand breaks (SSB) in the DNA.…”

Section: Introductionmentioning

confidence: 99%

Current Evidence and Future Perspectives about the Role of PARP Inhibitors in the Treatment of Thoracic Cancers

Parisi¹,

Rossi²,

Filippis³

et al. 2023

OTT

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In recent years, poly (ADP-ribose) polymerase (PARP) inhibition has become a promising therapeutic option for several tumors, especially for those harboring a BRCA 1–2 mutation or a deficit in the homologous recombination repair (HRR) pathway. Nevertheless, to date, PARP inhibitors are still not largely used for thoracic malignancies neither as a single agent nor in combination with other treatments. Recently, a deeper understanding of HRR mechanisms, alongside the development of new targeted and immunotherapy agents, particularly against HRR-deficient tumors, traced the path to new treatment strategies for many tumor types including lung cancer and malignant pleural mesothelioma. The aim of this review is to sum up the current knowledge about cancer-DNA damage response pathways inhibition and to update the status of recent clinical trials investigating the use of PARP inhibitors, either as monotherapy or in combination with other agents for the treatment of thoracic malignancies. We will also briefly discuss available evidence on Poly(ADP-Ribose) Glycohydrolase (PARG) inhibitors, a novel promising therapeutic option in oncology.

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Indazole as a privileged scaffold in drug discovery

Cui

2023

Privileged Scaffolds in Drug Discovery

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PARP inhibitors in small cell lung cancer: The underlying mechanisms and clinical implications

Cited by 5 publications

References 146 publications

PARP inhibitors combined with radiotherapy: are we ready?

PARP inhibitors combined with radiotherapy: are we ready?

Current Evidence and Future Perspectives about the Role of PARP Inhibitors in the Treatment of Thoracic Cancers

Indazole as a privileged scaffold in drug discovery

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