Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan, Italy.
Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Expert Rev Mol Diagn. 2021 Aug;21(8):757-766. doi: 10.1080/14737159.2021.1943365. Epub 2021 Jul 18.
: The treatment scenario of lung cancer is rapidly evolving through time. In parallel, growing evidence is accumulating on different mechanisms of treatment resistance. Inter- and intra-tumor heterogeneity define the spatial and temporal tumor clonal evolution, that is at the basis of tumor progression and resistance to anticancer treatments.: This review summarizes the available evidence on molecular heterogeneity in lung cancer, from diagnosis to the occurrence of treatment resistance. The application of novel molecular diagnostic methods to detect molecular heterogeneity, and the implications of understanding heterogeneity for drug development strategies are discussed, with focus on clinical relevance and impact on patients' survival.: The current knowledge of molecular heterogeneity allows to identify different molecular subgroups of patients within the same conventional tumor type. Deeper understanding of heterogeneity determinants and the possibility to comprehensively investigate tumor molecular patterns will lead to the development of personalized treatment approaches, with the final goal to overcome resistance and prolong survival in lung cancer patients.
: 肺癌的治疗方案随着时间的推移迅速发展。与此同时，越来越多的证据不断积累，揭示了不同的治疗耐药机制。肿瘤内和肿瘤间的异质性定义了空间和时间上的肿瘤克隆进化，这是肿瘤进展和对抗癌治疗耐药的基础。: 本综述总结了肺癌从诊断到治疗耐药发生过程中分子异质性的现有证据。讨论了应用新型分子诊断方法检测分子异质性，以及了解异质性对药物开发策略的意义，重点关注临床相关性和对患者生存的影响。: 目前对分子异质性的认识使得能够在同一常规肿瘤类型内识别不同的分子亚群患者。更深入地了解异质性决定因素，并有可能全面研究肿瘤分子模式，将导致制定个体化治疗方法，最终目标是克服耐药性并延长肺癌患者的生存时间。
