Gasser Martin, Waaga-Gasser Ana Maria
Department of Surgery I, University of Wuerzburg, Oberduerrbacher Str. 6, 97080, Wuerzburg, Germany.
Department of Surgery I, Molecular Oncology and Immunology, University of Wuerzburg, Oberduerrbacher Str. 6, 97080, Wuerzburg, Germany.
Adv Exp Med Biol. 2016;917:95-120. doi: 10.1007/978-3-319-32805-8_6.
The therapeutic arsenal in solid tumors comprises different anticancer strategies with diverse chemotherapeutic agents and a growing number of biological substances. Large clinical study-based chemotherapeutic protocols combined with biologicals have become an important component in (neo-) adjuvant therapy alongside surgery in solid cancers as well as radiation therapy in some instances. In recent years, monoclonal antibodies have entered the mainstream of cancer therapy. Their first use was as antagonists of oncogenic receptor tyrosine kinases, but today monoclonal antibodies have emerged as long-sought vehicles for the targeted delivery of potent chemotherapeutic agents and as powerful tools to manipulate anticancer immune responses. There is a growing number of FDA approved monoclonal antibodies and small molecules targeting specific types of cancer suggestive of the clinical relevance of this approach.Targeted cancer therapies , also referred to as personalized medicine, are being studied for use alone, in combination with other targeted therapies, and in combination with chemotherapy. The use of monoclonal antibodies in colorectal and gastric cancer for example have shown best outcome when combined with chemotherapy, even though single agent anti-EGFR antibodies seem to be active in particular setting of metastatic colorectal cancer patients. However, it is not well defined whether the addition of anti-VEGF - and anti-EGFR strategies to chemotherapy could improve outcome in those patients susceptible to colorectal cancer-related metastases resection. Among the most promising approaches to activating therapeutic antitumor immunity is the blockade of immune checkpoints, exemplified by the recently FDA-approved agent, Ipilimumab, an antibody that blocks the coinhibitory receptor CTLA-4. Capitalizing on the success of Ipilimumab, agents that target a second coinhibitory receptor, PD-1, or its ligand, PD-L1, are in clinical development. This section attempts to discuss recent progress of targeted agents and in tackling a more general target applicable to gastrointestinal cancer .
实体肿瘤的治疗手段包括使用不同的化疗药物和越来越多的生物制剂的多种抗癌策略。基于大型临床研究的化疗方案与生物制剂相结合，已成为实体癌（新）辅助治疗中的一个重要组成部分，在某些情况下还可与手术以及放射治疗联合使用。近年来，单克隆抗体已成为癌症治疗的主流。其最初用途是作为致癌受体酪氨酸激酶的拮抗剂，但如今单克隆抗体已成为人们长期寻求的强效化疗药物靶向递送载体以及操纵抗癌免疫反应的有力工具。越来越多的FDA批准的针对特定类型癌症的单克隆抗体和小分子表明了这种方法的临床相关性。靶向癌症治疗，也称为个性化医疗，正在被研究单独使用、与其他靶向治疗联合使用以及与化疗联合使用。例如，在结直肠癌和胃癌中使用单克隆抗体与化疗联合时显示出最佳疗效，尽管单药抗表皮生长因子受体（EGFR）抗体似乎在转移性结直肠癌患者的特定情况下具有活性。然而，对于那些易于进行结直肠癌相关转移灶切除的患者，在化疗中添加抗血管内皮生长因子（VEGF）和抗EGFR策略是否能改善预后尚未明确界定。激活治疗性抗肿瘤免疫的最有前景的方法之一是阻断免疫检查点，最近FDA批准的药物伊匹单抗就是一个例子，它是一种阻断共抑制受体细胞毒性T淋巴细胞相关抗原4（CTLA-4）的抗体。利用伊匹单抗的成功经验，靶向第二种共抑制受体程序性死亡蛋白1（PD-1）或其配体程序性死亡配体1（PD-L1）的药物正在进行临床开发。本节试图讨论靶向药物在治疗胃肠道癌方面的最新进展以及一个更通用的靶点。
