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精准肿瘤学:既非万灵药也非梦想。

Precision oncology: neither a silver bullet nor a dream.

作者信息

Sánchez Nora S, Mills Gordon B, Mills Shaw Kenna R

机构信息

Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Pharmacogenomics. 2017 Nov;18(16):1525-1539. doi: 10.2217/pgs-2017-0094. Epub 2017 Oct 24.

DOI:10.2217/pgs-2017-0094
PMID:29061079
Abstract

Precision oncology is not an illusion, nor is it the magic bullet that will eradicate all cancers. Precision oncology is simply another weapon in our growing armament against cancer. Rather than honing in on the failures of a relatively young field, one should advocate for integrating its successes into widespread clinical practice, especially for indications, such as: ABL, ALK, BRAF, BRCA1, BRCA2, EGFR, KIT, KRAS, PDGFRA, PDGFRB, ROS1, BCR-ABL, FLT3 and ROS1, where aberrations have been shown to alter responses to US FDA approved drugs - that is, level 1 data. Moreover, to truly assess the promise of precision oncology, we must first begin by defining our expectations for this field. Importantly, we must recognize that the conception of precision oncology arose as an antithesis of the 'one-size fits all' cancer therapeutics approach. Consequently, tools used for evaluating these conventional, large-scale trials, are not directly transferable for assessing nonconventional, smaller-scale trials needed for evaluating precision oncology. Hence, a thorough vetting of precision oncology as another tool of the trade, must first begin by reassessing our expectations for this field, as well as current clinical trial designs and end point measurements. Importantly, we must recognize that most targeted therapy approaches are in their infancy, with only monotherapy approaches being assessed and combination therapies likely being necessary to fulfill the promise of precision oncology.

摘要

精准肿瘤学并非幻想,也不是能根除所有癌症的神奇子弹。精准肿瘤学只是我们对抗癌症的不断扩充的武器库中的又一件武器。与其关注一个相对年轻领域的失败之处,人们更应该倡导将其成功经验融入广泛的临床实践,尤其是针对以下适应症:ABL、ALK、BRAF、BRCA1、BRCA2、EGFR、KIT、KRAS、PDGFRA、PDGFRB、ROS1、BCR-ABL、FLT3和ROS1,在这些方面,基因畸变已被证明会改变对美国食品药品监督管理局批准药物的反应——也就是说,有一级数据支持。此外,为了真正评估精准肿瘤学的前景,我们必须首先明确对这个领域的期望。重要的是,我们必须认识到,精准肿瘤学的概念是作为“一刀切”癌症治疗方法的对立面而产生的。因此,用于评估这些传统大规模试验的工具,不能直接用于评估评估精准肿瘤学所需的非传统小规模试验。所以,要将精准肿瘤学作为另一种行业工具进行全面审查,首先必须重新评估我们对这个领域的期望,以及当前的临床试验设计和终点测量方法。重要的是,我们必须认识到,大多数靶向治疗方法仍处于起步阶段,目前仅在评估单一疗法,而联合疗法可能是实现精准肿瘤学前景所必需的。

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