IrsiCaixa, Germans Trias i Pujol University Hospital, Badalona, Spain; Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA.
ESMO Open. 2021 Apr;6(2):100060. doi: 10.1016/j.esmoop.2021.100060. Epub 2021 Feb 26.
Precision medicine is now pivotal to design patients' specific treatment strategies with the aim of prolonging progression and overall survival. In this regard, invasive tumor tissue testing has so far been the golden standard for making cancer diagnosis, but has limitations. Cell-free tumor DNA (ctDNA), a form of liquid biopsy, is a noninvasive biomarker that can be isolated from patients' blood and other biofluids. An increasing body of evidence has demonstrated clinical utility of plasma ctDNA profiling to select patients for genomic-driven therapies. Analyses of mutations in plasma ctDNA have shown high accuracy and more rapid identification of mutations, allowing matching patients for specific therapies with equivalent clinical efficacy to that of the tissue profiling. In the clinical setting, ctDNA has been recently implemented to select patients with specific genomic alterations to targeted treatments, and a few molecular tests have been approved for use in non-small-cell lung, prostate, ovarian, and breast cancers. However, standardization of ctDNA collection, storage, and analysis methods would be critical to facilitate the wide adoption of ctDNA technology in routine clinical practice. This review summarizes how we can exploit ctDNA analysis to treat cancer patients, and explains how the results should be interpreted. In addition, we focus on how ctDNA could be used in the future as a marker of minimal residual disease to guide adjuvant therapy, as an immuno-oncology biomarker in patients treated with immune checkpoint blockade drugs, and as an early cancer detection marker to screen the asymptomatic population.
精准医学现在对于设计患者特定的治疗策略至关重要，目的是延长进展和总体生存。在这方面，侵入性肿瘤组织检测一直是癌症诊断的金标准，但存在局限性。游离肿瘤 DNA（ctDNA）是一种液体活检的非侵入性生物标志物，可以从患者的血液和其他生物液中分离出来。越来越多的证据表明，血浆 ctDNA 分析在选择接受基因组驱动治疗的患者方面具有临床实用性。对血浆 ctDNA 中的突变进行分析表明，其具有较高的准确性和更快的突变识别能力，使患者能够匹配特定的治疗方法，其临床疗效与组织分析相当。在临床环境中，ctDNA 最近已被用于选择具有特定基因组改变的患者接受靶向治疗，少数分子检测已被批准用于非小细胞肺癌、前列腺癌、卵巢癌和乳腺癌。然而，ctDNA 的采集、存储和分析方法的标准化对于促进 ctDNA 技术在常规临床实践中的广泛应用至关重要。这篇综述总结了我们如何利用 ctDNA 分析来治疗癌症患者，并解释了如何解释结果。此外，我们还重点介绍了 ctDNA 未来如何作为微小残留病的标志物来指导辅助治疗，作为免疫检查点阻断药物治疗患者的免疫肿瘤生物标志物，以及作为早期癌症检测标志物来筛查无症状人群。
