Division of Semeiotics and Medical Methodology, Department of Internal Medicine, University of Genoa, Italy.
Curr Cancer Drug Targets. 2012 May;12(4):316-28. doi: 10.2174/156800912800190956.
Personalized medicine emphasizes the practice of considering individual patient characteristics as opposed to that centered on standards derived from epidemiological studies which, by definition, do not take into account the variability of individuals within a given population. When applied to oncology, personalized medicine is an even more complex concept because it extends the variability beyond the individual patient to the individual tumor. Indeed, the great genotypic and phenotypic variability (both in primary and metastatic sites of cancer) the development of targeted therapies, and the growing availability of biological assays complicate the scenario of personalized medicine in the oncological field. In this paper we review the results of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) therapy in metastatic colorectal cancer (mCRC) in the context of tumor biology, delineating the future prospects of patient-tailored medicine in this area. In particular, we deal with EGFR inhibition by Cetuximab, a chimeric mouse human IgG1 mAb, and panitumumab, a fully human IgG2 mAb. We discuss the clinical impact of anti-EGFR mAbs on wild-type (WT) KRAS mCRC, also taking into account the feasibility of novel multi-marker approaches to treatment decision-making, aimed at increasing the predictive power of pre-therapy biomarkers. Experimental topics and fields of ongoing research, such as targeting microRNAs (miRNAs) with novel anticancer drugs and epigenetics in CRC are also addressed.
个体化医学强调考虑个体患者特征的实践,而不是以流行病学研究为中心的标准,这些标准根据定义,并未考虑到特定人群中个体的可变性。当应用于肿瘤学领域时,个体化医学更是一个更为复杂的概念,因为它将可变性从个体患者扩展到个体肿瘤。事实上,由于基因型和表型的巨大变异性(包括癌症的原发和转移部位)、靶向治疗的发展以及生物测定法的日益普及,使得肿瘤学领域个体化医学的情况更加复杂。在本文中,我们根据肿瘤生物学的情况,回顾了抗表皮生长因子受体(EGFR)单克隆抗体(mAb)治疗转移性结直肠癌(mCRC)的结果,阐述了该领域患者定制药物的未来前景。特别是,我们讨论了西妥昔单抗(一种嵌合鼠人 IgG1 mAb)和帕尼单抗(一种完全人 IgG2 mAb)对 EGFR 的抑制作用。我们讨论了抗 EGFR mAb 对野生型(WT)KRAS mCRC 的临床影响,同时还考虑了新型多标志物治疗决策方法的可行性,旨在提高治疗前生物标志物的预测能力。本文还涉及了实验课题和正在进行的研究领域,如用新型抗癌药物靶向 microRNAs(miRNAs)和 CRC 的表观遗传学。