Unique molecular landscapes in cancer: implications for individualized, curated drug combinations.
Unique molecular landscapes in cancer: implications for individualized, curated drug combinations.
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DOI：
10.1158/0008-5472.can-14-2329
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发表时间：
2014-12-15
期刊：
影响因子：
11.2
通讯作者：
Kurzrock R
中科院分区：
文献类型：
--
作者：
Wheler J;Lee JJ;Kurzrock R
随着分子生物学中越来越尖端的技术和分析患者肿瘤的“组学”平台，人们正在观察到癌症中更多的分子多样性和复杂性。最近，我们注意到基于下一代测序(NGS)分析的一组转移性乳腺癌患者的独特基因组特征；在57名连续的患者中，没有两名患者具有相同的分子组合。因此，应用基因组学似乎代表了一种颠覆性的创新，因为它揭示了转移性癌症的异质性，这种异质性可能不适合规范的临床试验和实践范式。在认识到患者有独特的肿瘤情况后，我们的传统临床试验系统(基于共同特征来选择患者以评估药物)与基于针对每个患者的经过精心管理的个性化药物组合的最佳治疗(以患者为中心的方法)之间可能存在“不匹配”。
With increasing lysophisticated technologies in molecular biology and ‘omic’ platforms to analyze patients’ tumors, more molecular diversity and complexity in cancer are being observed. Recently, we noted unique genomic profiles in a group of patients with metastatic breast cancer based on an analysis with next generation sequencing (NGS); amongst 57 consecutive patients, no two had the same molecular portfolio. Applied genomics therefore appears to represent a disruptive innovation in that it unveils a heterogeneity to metastatic cancer that may be ill suited to canonical clinical trials and practice paradigms. Upon recognizing that patients have unique tumor landscapes, it is possible that there may be a ‘mismatch’ between our traditional clinical trials system that selects patients based on common characteristics in order to evaluate a drug (drug-centric approach), and optimal treatment based on curated, individualized drug combinations for each patient (patient-centric approach).