Correlations between pathogenic variants in <scp>DNA</scp> repair genes and anticancer treatment efficacy in stage <scp>IV</scp> non‐small cell lung cancer: A large real‐world cohort and review of the literature

Averbuch, Itamar; Tschernichovsky, Roi; Icht, Oded; Goldstein, Daniel A.; Mutai, Raz; Dudnik, Elizabeth; Rotem, Ofer; Peled, Nir; Allen, Aaron M.; Laufer‐Geva, Smadar; Goldberg, Yael; Zer, Alona

doi:10.1111/1759-7714.14902

Cited by 2 publications

(1 citation statement)

References 32 publications

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“…For example, DNA damage response pathway-altered biliary tract cancers exhibited favorable chemotherapy responses ( 123 ). In the stage 4 non-small cell lung cancer (NSCLC), pathogenic variants in DDR pathway genes was associated with higher efficacy of radiotherapy and ICIs ( 124 ). The efficacy of chemotherapy can be reduced by STING through suppressing DDR and genotoxicity and DNA instability ( 125 ).…”

Section: Cell Cycle Checkpoint and Dna Damage Repair Pathway Impacts ...mentioning

confidence: 99%

Immunogenic chemotherapy: great potential for improving response rates

Huang,

Ren,

Yang

et al. 2023

Front. Oncol.

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The activation of anti-tumor immunity is critical in treating cancers. Recent studies indicate that several chemotherapy agents can stimulate anti-tumor immunity by inducing immunogenic cell death and durably eradicate tumors. This suggests that immunogenic chemotherapy holds great potential for improving response rates. However, chemotherapy in practice has only had limited success in inducing long-term survival or cure of cancers when used either alone or in combination with immunotherapy. We think that this is because the importance of dose, schedule, and tumor model dependence of chemotherapy-activated anti-tumor immunity is under-appreciated. Here, we review immune modulation function of representative chemotherapy agents and propose a model of immunogenic chemotherapy-induced long-lasting responses that rely on synergetic interaction between killing tumor cells and inducing anti-tumor immunity. We comb through several chemotherapy treatment schedules, and identify the needs for chemotherapy dose and schedule optimization and combination therapy with immunotherapy when chemotherapy dosage or immune responsiveness is too low. We further review tumor cell intrinsic factors that affect the optimal chemotherapy dose and schedule. Lastly, we review the biomarkers indicating responsiveness to chemotherapy and/or immunotherapy treatments. A deep understanding of how chemotherapy activates anti-tumor immunity and how to monitor its responsiveness can lead to the development of more effective chemotherapy or chemo-immunotherapy, thereby improving the efficacy of cancer treatment.

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Section: Cell Cycle Checkpoint and Dna Damage Repair Pathway Impacts ...mentioning

confidence: 99%

Immunogenic chemotherapy: great potential for improving response rates

Huang,

Ren,

Yang

et al. 2023

Front. Oncol.

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Correlations between pathogenic variants in DNA repair genes and anticancer treatment efficacy in stage IV non‐small cell lung cancer: A large real‐world cohort and review of the literature

et al. 2023

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Background Mutations in genes involved in DNA damage repair (DDR), a hallmark of cancer, are associated with increased cancer cell sensitivity to certain therapies. This study sought to evaluate the association of DDR pathogenic variants with treatment efficacy in patients with advanced non‐small cell lung cancer (NSCLC). Methods A retrospective cohort of consecutive patients with advanced NSCLC attending a tertiary medical center who underwent next‐generation sequencing in 01/2015‐8/2020 were clustered according to DDR gene status and compared for overall response rate (ORR), progression‐free survival (PFS) (patients receiving systemic therapy), local PFS (patients receiving definitive radiotherapy), and overall survival (OS) using log‐rank and Cox regression analyses. Results Of 225 patients with a clear tumor status, 42 had a pathogenic/likely pathogenic DDR variant (pDDR), and 183 had no DDR variant (wtDDR). Overall survival was similar in the two groups (24.2 vs. 23.1 months, p = 0.63). The pDDR group had a higher median local PFS after radiotherapy (median 45 months vs. 9.9 months, respectively; p = 0.044), a higher ORR (88.9% vs. 36.2%, p = 0.04), and a longer median PFS (not reached vs. 6.0 months, p = 0.01) in patients treated with immune checkpoint blockade. There was no difference in ORR, median PFS, and median OS in patients treated with platinum‐based chemotherapy. Conclusion Our retrospective data suggest that in patients with stage 4 NSCLC, pathogenic variants in DDR pathway genes may be associated with higher efficacy of radiotherapy and immune checkpoint inhibitors (ICIs). This should be further explored prospectively.

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Correlations between pathogenic variants in DNA repair genes and anticancer treatment efficacy in stage IV non‐small cell lung cancer: A large real‐world cohort and review of the literature

Cited by 2 publications

References 32 publications

Immunogenic chemotherapy: great potential for improving response rates

Immunogenic chemotherapy: great potential for improving response rates

Correlations between pathogenic variants in DNA repair genes and anticancer treatment efficacy in stage IV non‐small cell lung cancer: A large real‐world cohort and review of the literature

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