Rass K, Hassel J C
Clinic for Dermatology, Venerology and Allergology, The Saarland University Hospital, Homburg, Germany.
G Ital Dermatol Venereol. 2009 Feb;144(1):61-78.
Melanoma is one of the most aggressive forms of cancer with a continuously growing incidence worldwide. Survival mainly depends on primary tumor thickness, ulceration and sentinel node status at the time of diagnosis. Adjuvant therapies with interferons are able to prolong the recurrence-free survival, but the effects on overall survival are limited. Once, melanoma has metastasized to distant sites, the prognosis is fatal with median survival times between 7 and 9 months. Albeit removal of localized distant metastases is currently the most effective approach in metastatic melanoma in particular cases, chemo- and chemoimmunotherapy has to be regarded as standard treatment in the majority of patients. However, all available cytotoxic drugs and combinations applied so far have only a small impact on overall survival, if any. A fundamental cause of the limited efficacy of chemotherapy in advanced melanoma has to be seen in chemoresistance mechanisms. In melanoma, the intrinsic and mainly anti-apoptotic resistance, due to the physiological role of the UV exposed melanocytes, is prevailing. Further resistance mechanisms discussed in melanoma are DNA repair, multidrug transporter and the existence of cancer stem cells. Promising therapeutic options accrue from the growing insights into signaling pathways of melanoma that cause chemo- and apoptosis-resistance. The development of drugs targeting those mechanisms and their administration in combination with chemotherapy is currently one of the fascinating novel treatment approaches in melanoma.
黑色素瘤是最具侵袭性的癌症形式之一，在全球范围内其发病率持续上升。生存率主要取决于诊断时原发性肿瘤的厚度、溃疡情况以及前哨淋巴结状态。干扰素辅助治疗能够延长无复发生存期，但对总生存期的影响有限。一旦黑色素瘤转移至远处，预后凶险，中位生存期在7至9个月之间。尽管在特定病例中，切除局部远处转移灶目前是转移性黑色素瘤最有效的治疗方法，但在大多数患者中，化疗和化疗免疫疗法仍被视为标准治疗。然而，迄今为止应用的所有细胞毒性药物及其联合用药对总生存期的影响（如果有影响的话）都很小。化疗在晚期黑色素瘤中疗效有限的一个根本原因在于化疗耐药机制。在黑色素瘤中，由于紫外线暴露的黑素细胞的生理作用，内在的、主要是抗凋亡的耐药性占主导地位。黑色素瘤中讨论的其他耐药机制包括DNA修复、多药转运蛋白以及癌症干细胞的存在。对导致化疗耐药和凋亡抵抗的黑色素瘤信号通路的深入了解带来了有前景的治疗选择。针对这些机制开发药物并将其与化疗联合应用，目前是黑色素瘤中令人着迷的新型治疗方法之一。
