Bersani Francesca, Morena Deborah, Picca Francesca, Morotti Alessandro, Tabbò Fabrizio, Bironzo Paolo, Righi Luisella, Taulli Riccardo
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
Department of Oncology, University of Torino, 10043 Orbassano, Italy.
Transl Lung Cancer Res. 2020 Dec;9(6):2629-2644. doi: 10.21037/tlcr-20-189.
Lung cancer currently stands out as both the most common and the most lethal type of cancer, the latter feature being partly explained by the fact that the majority of lung cancer patients already display advanced disease at the time of diagnosis. In recent years, the development of specific tyrosine kinase inhibitors (TKI) for the therapeutic benefit of patients harboring certain molecular aberrations and the introduction of prospective molecular profiling in the clinical practice have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). However, the identification of the best strategies to enhance treatment effectiveness and to avoid the critical phenomenon of drug tolerance and acquired resistance in patients with lung cancer still remains an unmet medical need. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two complementary approaches to define tumor heterogeneity and clonal evolution in a non-invasive manner and to perform functional studies on metastatic cells. Finally, the recent discovery that the tumor microenvironment architecture can be faithfully recapitulated represents a novel pre-clinical frontier with the potential to optimize more effective immunology-based precision therapies that could rapidly move forward to the clinic.
肺癌目前是最常见且最致命的癌症类型，后者部分原因在于大多数肺癌患者在诊断时就已处于疾病晚期。近年来，针对具有特定分子异常的患者开发的特异性酪氨酸激酶抑制剂（TKI）以及临床实践中引入的前瞻性分子分析，彻底改变了晚期非小细胞肺癌（NSCLC）的治疗方式。然而，确定最佳策略以提高治疗效果并避免肺癌患者出现药物耐受性和获得性耐药这一关键现象，仍然是尚未满足的医疗需求。循环肿瘤细胞（CTC）和循环肿瘤DNA（ctDNA）是两种互补的方法，可用于以非侵入性方式定义肿瘤异质性和克隆进化，并对转移细胞进行功能研究。最后，肿瘤微环境结构能够被忠实地重现这一最新发现代表了一个新的临床前前沿领域，有可能优化更有效的基于免疫的精准疗法，并能迅速进入临床应用。
