PDF(Pubmed)
Abstract：
Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide. In detail, basal cell carcinoma (BCC) is the most frequent malignancy in the fair-skinned population. The incidence of BCC remains difficult to assess due to the poor registration practice; however, it has been increasing in the last few years. Approximately, 85% of sporadic BCCs carry mutations in Hedgehog pathway genes, especially in PTCH, SUFU and SMO genes, which lead to the aberrant activation of GLI transcriptional factors, typically silent in cells of adult individuals. The management of advanced BCC (aBCC), both metastatic (mBCC) and locally advanced BCC (laBCC), not candidates for surgical excision or radiotherapy, remains challenging. The discovery of mutations in the Hh signaling pathway has paved the way for the development of Hh pathway inhibiting agents, such as vismodegib and sonidegib, which have represented a breakthrough in the aBCC management. However, the use of these agents is limited by the frequent occurrence of adverse events or the development of drug resistance. In this review, we thoroughly describe the current knowledge regarding the available options for the pharmacological management of aBCCs and provide a forward-looking update on novel therapeutic strategies that could enrich the therapeutic armamentarium of BCC in the near future.
摘要：
非黑素瘤皮肤癌(NMSCs)是全世界最常见的人类肿瘤。详细来说,基底细胞癌（BCC）是皮肤白皙人群中最常见的恶性肿瘤。由于登记做法不佳，BCC的发生率仍然难以评估；然而，在过去的几年里，它一直在增加。大约,85%的散发性BCCs携带Hedgehog通路基因突变，尤其是在PTCH中，SUFU和SMO基因，导致GLI转录因子的异常激活，通常在成年个体的细胞中沉默。高级BCC（aBCC）的管理，转移性（mBCC）和局部晚期BCC（laBCC），不是手术切除或放射治疗的候选人，仍然具有挑战性。Hh信号通路突变的发现为Hh信号通路抑制剂的发展铺平了道路,比如vismodegib和sonidegib,这代表了aBCC管理的突破。然而,这些药物的使用受到频繁发生的不良事件或耐药性发展的限制。在这次审查中,我们全面描述了目前有关aBCC药理学管理的可用选择的知识,并提供了关于新的治疗策略的前瞻性更新,这些策略可以在不久的将来丰富BCC的治疗性医疗设备.
