Bailey Ann M, Mao Yong, Zeng Jia, Holla Vijaykumar, Johnson Amber, Brusco Lauren, Chen Ken, Mendelsohn John, Routbort Mark J, Mills Gordon B, Meric-Bernstam Funda
Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Discov Med. 2014 Feb;17(92):101-14.
There has been growing interest in biomarker-driven personalized cancer therapy, also known as precision medicine. Recently, dozens of molecular tests, including next generation sequencing, have been developed to detect biomarkers that have the potential to predict response of cancers to particular targeted therapies. However, detection of cancer-related biomarkers is only the first step in the battle. Deciding what therapy options to pursue can also be daunting, especially when tumors harbor more than one potentially actionable aberration. Further, different mutations/variants in a single gene may have different functional consequences, and response to targeted agents may be context dependent. However, early clinical trials with new molecular entities are increasingly conducted in a biomarker-selected fashion, and even when trials are not biomarker-selected, much effort is placed on enrolling patients onto clinical trials where they have the highest probability of response. We review available molecular tests and therapy discerning tools, including tools available for assessing functional consequences of molecular alterations and tools for finding applicable clinical trials, which exist to help bridge the gap between detection of cancer-related biomarker to the initiation of biomarker-matched targeted therapies.
生物标志物驱动的个性化癌症治疗,即精准医学,已引发越来越多的关注。最近,包括新一代测序在内的数十种分子检测方法已被开发出来,用于检测有可能预测癌症对特定靶向治疗反应的生物标志物。然而,癌症相关生物标志物的检测仅仅是这场战斗的第一步。决定采取何种治疗方案也可能令人望而生畏,尤其是当肿瘤存在不止一种潜在可操作的异常时。此外,单个基因中的不同突变/变体可能具有不同的功能后果,并且对靶向药物的反应可能取决于具体情况。然而,新分子实体的早期临床试验越来越多地以生物标志物选择的方式进行,即使试验没有进行生物标志物选择,也会付出很大努力将患者纳入最有可能产生反应的临床试验。我们回顾了现有的分子检测和治疗辨别工具,包括用于评估分子改变功能后果的工具以及用于寻找适用临床试验的工具,这些工具旨在帮助弥合癌症相关生物标志物检测与启动生物标志物匹配的靶向治疗之间的差距。