Department of Pathology and Microbiology, University of Nebraska Medical Center, 85900 Nebraska Medical Center, Omaha, NE 68198-5900, USA.
Curr Mol Med. 2011 Oct;11(7):553-63. doi: 10.2174/156652411800615153.
Metastatic melanoma is one of the most intractable tumors, with all current regimens showing limited survival impact. Failure of most agents is attributed to development of therapy resistance. Accumulated evidence points to the apoptotic defect of melanoma cells and the surge of survival signals stimulated by cytotoxic drugs, as a way that tumors circumvent cytotoxic chemotherapy. An overview of inhibitors developed against these growth/survival factors, which are potential partners to be combined with systemic chemotherapy, will be discussed. The escape mechanism from molecular inhibitors also suggests a "vertical" or "horizontal" combination of molecularly targeted therapies. A better understanding of the interactions between simultaneously used regimens and of the rationale for combination therapy will provide new insights to improve survival and quality of life in patients with advanced melanoma.
转移性黑色素瘤是最难治疗的肿瘤之一，目前所有的治疗方案显示对生存的影响有限。大多数药物的失败归因于治疗耐药性的发展。越来越多的证据表明黑色素瘤细胞的凋亡缺陷和细胞毒性药物刺激的存活信号的激增，这是肿瘤规避细胞毒性化疗的一种方式。本文将综述针对这些生长/存活因素的抑制剂的开发情况，这些抑制剂可能是与全身化疗联合应用的潜在伙伴。从分子抑制剂中逃脱的机制也提示了分子靶向治疗的“垂直”或“水平”联合。更好地理解同时使用的方案之间的相互作用以及联合治疗的原理，将为改善晚期黑色素瘤患者的生存和生活质量提供新的见解。
