Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
J Intern Med. 2015 Feb;277(2):201-217. doi: 10.1111/joim.12321.
Personalized medicine involves the selection of the safest and most effective pharmacological treatment based on the molecular characteristics of the patient. In the case of anticancer drugs, tumour cell alterations can have a great impact on drug activity and, in fact, most biomarkers predicting response originate from these cells. On the other hand, the risk of developing severe toxicity may be related to the genetic background of the patient. Thus, understanding the molecular characteristics of both the tumour and the patient, and establishing their relation with drug outcomes will be critical for the identification of predictive biomarkers and to provide the basis for individualized treatments. This is a complex scenario where multiple genes as well as pathophysiological and environmental factors are important; in addition, tumours exhibit large inter- and intraindividual variability in space and time. Against this background, the huge amounts of biological and genetic data generated by the high-throughput technologies will facilitate pharmacogenomic progress, suggest novel druggable molecules and support the design of future strategies aimed at disease control. Here, we will review the current challenges and opportunities for pharmacogenomic studies in oncology, as well as the clinically established biomarkers. Lung and renal cancer, two areas in which huge progress has been made in the last decade, will be used to illustrate advances in personalized cancer treatment; we will review EGFR mutation as the paradigm of targeted therapies in lung cancer, and discuss the dissection of lung cancer into clinically relevant molecular subsets and novel advances that suggest an important role of single nucleotide polymorphisms in the response to antiangiogenic agents, as well as the challenges that remain in these fields. Finally, we will present new approaches and future prospects for personalizing medicine in oncology.
个体化医学涉及根据患者的分子特征选择最安全、最有效的药物治疗。在抗癌药物的情况下，肿瘤细胞的改变可能会对药物活性产生重大影响，事实上，大多数预测反应的生物标志物都来源于这些细胞。另一方面，患者发生严重毒性的风险可能与遗传背景有关。因此，了解肿瘤和患者的分子特征，并建立它们与药物结果的关系，对于识别预测性生物标志物和为个体化治疗提供基础至关重要。这是一个复杂的情况，多个基因以及病理生理和环境因素都很重要；此外，肿瘤在空间和时间上表现出很大的个体间和个体内变异性。在此背景下，高通量技术产生的大量生物和遗传数据将促进药物基因组学的发展，提示新的可药物治疗的分子，并支持旨在控制疾病的未来策略的设计。在这里，我们将回顾肿瘤药物基因组学研究的当前挑战和机遇，以及临床已建立的生物标志物。肺癌和肾癌是过去十年中取得巨大进展的两个领域，将用于说明个性化癌症治疗的进展；我们将回顾 EGFR 突变作为肺癌靶向治疗的范例，并讨论将肺癌分为具有临床意义的分子亚型以及提示单核苷酸多态性在抗血管生成剂反应中的重要作用的新进展，以及这些领域中仍然存在的挑战。最后，我们将介绍肿瘤个体化医学的新方法和未来前景。
