Gastric cancer, a major global health concern, poses challenges in effective treatment, notably due to chemoresistance. This study investigates the role of growth/differentiation factor-15 (GDF-15) in mitochondrial dysfunction and its impact on cisplatin sensitivity in gastric cancer cells. In this issue of The FEBS Journal, Wang et al. demonstrate that GDF15 upregulation is associated with cisplatin insensitivity, mediated by the ATF4-CHOP pathway and reactive oxygen species-activated general control nonderepressible 2 [Wang S-F et al. (2023) FEBS J, https://doi.org/10.1111/febs.16992]. Connecting these insights, we explore the broader implications of GDF15 expression in the aging-cancer axis, particularly its involvement in cellular senescence and the senescence-associated secretory phenotype (SASP). This study suggests that GDF15 released by senescent cells could contribute to tumor progression, indicating potential avenues for therapeutic intervention by targeting senescent cells and their SASP. While the study provides valuable insights into mitigating cisplatin resistance, further research is crucial to fully understand the role of GDF15 in the tumor microenvironment and its potential feedback loops promoting tumorigenesis.

中文翻译：

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胃癌中的线粒体功能障碍和顺铂敏感性：GDF15 作为主力

胃癌是全球主要的健康问题，对有效治疗提出了挑战，特别是由于化疗耐药性。本研究探讨生长/分化因子 15 (GDF-15) 在线粒体功能障碍中的作用及其对胃癌细胞顺铂敏感性的影响。在本期FEBS Journal中，Wang等人。证明 GDF15 上调与顺铂不敏感性相关，由 ATF4-CHOP 途径和活性氧激活的一般控制非阻抑性 2 介导 [Wang SF等人 2017]。（2023）FEBS J，https://doi.org/10.1111/febs.16992]。将这些见解联系起来，我们探讨了 GDF15 表达在衰老-癌症轴中的更广泛影响，特别是它在细胞衰老和衰老相关分泌表型 (SASP) 中的参与。这项研究表明，衰老细胞释放的 GDF15 可能有助于肿瘤进展，这表明通过靶向衰老细胞及其 SASP 进行治疗干预的潜在途径。虽然该研究为减轻顺铂耐药性提供了宝贵的见解，但进一步的研究对于充分了解 GDF15 在肿瘤微环境中的作用及其促进肿瘤发生的潜在反馈回路至关重要。