Offin Michael, Chabon Jacob J, Razavi Pedram, Isbell James M, Rudin Charles M, Diehn Maximilian, Li Bob T
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA; Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
J Oncol. 2017;2017:4517834. doi: 10.1155/2017/4517834. Epub 2017 Mar 14.
Genetic sequencing of malignancies has become increasingly important to uncover therapeutic targets and capture the tumor's dynamic changes to drug sensitivity and resistance through genomic evolution. In lung cancers, the current standard of tissue biopsy at the time of diagnosis and progression is not always feasible or practical and may underestimate intratumoral heterogeneity. Technological advances in genetic sequencing have enabled the use of circulating tumor DNA (ctDNA) analysis to obtain information on both targetable mutations and capturing real-time Darwinian evolution of tumor clones and drug resistance mechanisms under selective therapeutic pressure. The ability to analyze ctDNA from plasma, CSF, or urine enables a comprehensive view of cancers as systemic diseases and captures intratumoral heterogeneity. Here, we describe these recent advances in the setting of lung cancers and advocate for further research and the incorporation of ctDNA analysis in clinical trials of targeted therapies. By capturing genomic evolution in a noninvasive manner, liquid biopsy for ctDNA analysis could accelerate therapeutic discovery and deliver the next leap forward in precision medicine for patients with lung cancers and other solid tumors.
恶性肿瘤的基因测序对于揭示治疗靶点以及通过基因组进化了解肿瘤对药物敏感性和耐药性的动态变化变得越来越重要。在肺癌中，目前诊断和病情进展时组织活检的标准并不总是可行或实际的，而且可能会低估肿瘤内的异质性。基因测序技术的进步使得利用循环肿瘤DNA（ctDNA）分析成为可能，从而获得关于可靶向突变的信息，并捕捉肿瘤克隆在选择性治疗压力下的实时达尔文进化以及耐药机制。分析来自血浆、脑脊液或尿液中的ctDNA的能力，能够全面了解癌症作为一种全身性疾病的情况，并捕捉肿瘤内的异质性。在此，我们描述了肺癌领域的这些最新进展，并倡导进一步研究以及将ctDNA分析纳入靶向治疗的临床试验中。通过以非侵入性方式捕捉基因组进化，用于ctDNA分析的液体活检可以加速治疗发现，并为肺癌和其他实体瘤患者的精准医学带来下一次飞跃。
