Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA, 91010, USA.
Department of Internal Medicine, University of Utah, 30 N 1900 E, Rm 4C104, Salt Lake City, UT, 84132, USA.
Curr Treat Options Oncol. 2018 Feb 20;19(2):10. doi: 10.1007/s11864-018-0530-4.
Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) is a novel technology that can complement tumor tissue NGS and has the potential to influence diagnosis and treatment of both localized and metastatic renal cell carcinoma (mRCC). ctDNA NGS is an attractive alternative to tumor tissue NGS because it circumvents the need for repeated, invasive tissue biopsies while providing a contemporary mutational profile of a patient's tumors. While the role of ctDNA NGS in non-small cell lung cancer and colorectal cancer is well established, studies of ctDNA NGS in mRCC are only hypothesis-generating to date. In the localized RCC setting, ctDNA has demonstrated potential as a surveillance biomarker for disease recurrence. Earlier detection of mRCC, prior to the onset of symptoms, may lead to improved clinical outcomes. NGS of ctDNA in mRCC is even more promising in patients with metastatic disease. The majority of patients with mRCC have detectable ctDNA. Thus, ctDNA could be used to select patients for biomarker-guided clinical trials, such as savolitinib in MET-positive papillary RCC. Furthermore, studies have shown that the mutational profile of mRCC in ctDNA evolves after treatment progression. The most exciting potential role for ctDNA in mRCC is as a predictive biomarker for response to immunotherapy. Studies have shown that tumor mutational burden (TMB) is predictive of response to immune checkpoint inhibitors, and hypermutated ctDNA can act as a surrogate biomarker for TMB and response to immunotherapy. While studies of ctDNA in RCC are still in their infancy, there are many promising roles for ctDNA in localized and metastatic RCC.
下一代测序（NGS）的循环肿瘤 DNA（ctDNA）是一种新型技术，可以补充肿瘤组织 NGS，并有可能影响局部和转移性肾细胞癌（mRCC）的诊断和治疗。ctDNA NGS 是肿瘤组织 NGS 的一种有吸引力的替代方法，因为它避免了对重复、侵入性组织活检的需求，同时提供了患者肿瘤的当代突变谱。虽然 ctDNA NGS 在非小细胞肺癌和结直肠癌中的作用已经得到证实，但迄今为止，ctDNA NGS 在 mRCC 中的研究只是假设性的。在局部 RCC 环境中，ctDNA 已被证明是疾病复发的潜在监测生物标志物。更早地检测 mRCC，在症状出现之前，可能会改善临床结果。ctDNA 的 NGS 在转移性疾病患者中更有前途。大多数 mRCC 患者都有可检测到的 ctDNA。因此，ctDNA 可用于选择接受生物标志物指导的临床试验的患者，例如在 MET 阳性乳头状 RCC 中使用 savolitinib。此外，研究表明，ctDNA 中 mRCC 的突变谱在治疗进展后会发生演变。ctDNA 在 mRCC 中最令人兴奋的潜在作用是作为免疫治疗反应的预测生物标志物。研究表明，肿瘤突变负荷（TMB）是对免疫检查点抑制剂反应的预测因子，而高度突变的 ctDNA 可以作为 TMB 和免疫治疗反应的替代生物标志物。虽然 RCC 中的 ctDNA 研究仍处于起步阶段，但 ctDNA 在局部和转移性 RCC 中有许多有前途的作用。
