The Thoracic Surgery Oncology Laboratory and The International Mesothelioma Program, Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Int J Mol Sci. 2022 Nov 3;23(21):13422. doi: 10.3390/ijms232113422.
Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20-40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as , , and . Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets.
胸膜间皮瘤 (PM) 是一种罕见且侵袭性的疾病，起源于覆盖胸膜腔的间皮细胞。大约 80%的 PM 患者有石棉暴露史。从石棉暴露到诊断的潜伏期长达 20-40 年，这表明 PM 的肿瘤发生需要多个体细胞遗传改变。PM 的基因组图谱表现为与肿瘤抑制基因失活相关的肿瘤内和肿瘤间异质性，如 、 和 等。目前的全身治疗方法仅显示出有限的疗效，没有一种方法被批准用于复发性 PM 患者。对 PM 分子图谱的深入了解促进了几项基于生物标志物的临床试验，但迄今为止，没有用于靶向治疗的预测性生物标志物在临床中使用。最近在 PM 遗传学方面的进展为未来成功的分子策略提供了希望。在这里，我们总结了 PM 发病机制的分子机制，并回顾了潜在的治疗靶点。
