The Institute of Cancer Research, London, UK.
The Royal Marsden NHS Foundation Trust, London, UK.
Nat Rev Clin Oncol. 2021 Jul;18(7):454-467. doi: 10.1038/s41571-021-00489-x. Epub 2021 Mar 24.
Anticancer drug development is a costly and protracted activity, and failure at late phases of clinical testing is common. We have previously proposed the Pharmacological Audit Trail (PhAT) intended to improve the efficiency of drug development, with a focus on the use of tumour tissue-based biomarkers. Blood-based 'liquid biopsy' approaches, such as targeted or whole-genome sequencing studies of plasma circulating cell-free tumour DNA (ctDNA) and circulating tumour cells (CTCs), are of increasing relevance to this drug development paradigm. Liquid biopsy assays can provide quantitative and qualitative data on prognostic, predictive, pharmacodynamic and clinical response biomarkers, and can also enable the characterization of disease evolution and resistance mechanisms. In this Perspective, we examine the promise of integrating liquid biopsy analyses into the PhAT, focusing on the current evidence, advances, limitations and challenges. We emphasize the continued importance of analytical validation and clinical qualification of circulating tumour biomarkers through prospective clinical trials.
抗癌药物的开发是一项成本高昂且漫长的工作，在临床试验的后期失败是很常见的。我们之前提出了药理学审计追踪（PhAT），旨在提高药物开发的效率，重点是使用肿瘤组织为基础的生物标志物。基于血液的“液体活检”方法，如针对血浆中循环无细胞肿瘤 DNA（ctDNA）和循环肿瘤细胞（CTC）的靶向或全基因组测序研究，与这种药物开发模式的相关性越来越大。液体活检分析可以提供预后、预测、药效学和临床反应生物标志物的定量和定性数据，还可以实现疾病演变和耐药机制的特征描述。在这篇观点文章中，我们探讨了将液体活检分析纳入 PhAT 的前景，重点关注当前的证据、进展、局限性和挑战。我们强调通过前瞻性临床试验对循环肿瘤生物标志物进行分析验证和临床验证的持续重要性。
