Grüllich Carsten, von Kalle Christof
Department of Translational Oncology, National Center for Tumor Diseases, Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Germany.
Onkologie. 2012;35 Suppl 1:4-7. doi: 10.1159/000334825. Epub 2012 Jan 20.
Increasing understanding of molecular carcinogenesis has begun to change paradigms in oncology. On the diagnostic side, the characterization of key mutations and molecular pathways responsible for tumor development and progression has led to the identification of a large number of potential targets for diagnostic and therapeutic intervention. On the treatment and prevention side, molecular analysis will be of even greater importance for guiding individualized therapy. Diagnostics of molecular lesions present in each tumor will become a key feature of future clinical care. This will allow prediction of response with substantially increased accuracy, stratification of particular patient groups, and eventually personalization of therapy. Striking examples of molecular targeted therapies that have already been established in clinical practice include tyrosine kinase inhibitors in chronic myelogenous leukemia and gastrointestinal stromal tumors, epidermal growth factor receptor (EGFR) inhibition in EGFR-mutated lung cancer, HER2/neu blockade in HER2/neu-positive breast cancer, and anaplastic lymphoma kinase (ALK) inhibitors in lung cancer with EML4-ALK fusion. The scientific development along this line will change the approach to tumor diseases in the future. Patients will be treated according to the specific molecular profiles found in the individual tumor tissue and preferentially with targeted substances, if available.
对分子致癌作用认识的不断加深已开始改变肿瘤学的范式。在诊断方面,对导致肿瘤发生和进展的关键突变及分子途径的表征,已促使人们识别出大量用于诊断和治疗干预的潜在靶点。在治疗和预防方面,分子分析对于指导个体化治疗将更为重要。对每个肿瘤中存在的分子病变进行诊断将成为未来临床护理的关键特征。这将使反应预测的准确性大幅提高,对特定患者群体进行分层,并最终实现治疗的个性化。已在临床实践中确立的分子靶向治疗的显著例子包括用于慢性粒细胞白血病和胃肠道间质瘤的酪氨酸激酶抑制剂、用于表皮生长因子受体(EGFR)突变型肺癌的EGFR抑制、用于HER2/neu阳性乳腺癌的HER2/neu阻断,以及用于伴有EML4-ALK融合的肺癌的间变性淋巴瘤激酶(ALK)抑制剂。沿着这条路线的科学发展将改变未来肿瘤疾病的治疗方法。患者将根据在个体肿瘤组织中发现的特定分子特征进行治疗,如果有可用的靶向物质,则优先使用靶向物质。