Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.
Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.
复制标题
DOI：
10.1002/mc.22690
复制
发表时间：
2017-12
影响因子：
4.6
通讯作者：
Athar M
中科院分区：
文献类型：
--
作者：
Bakshi A;Chaudhary SC;Rana M;Elmets CA;Athar M
皮肤基底细胞癌 (BCC) 是由异常的刺猬信号传导驱动的。因此，通过小分子（例如 vismodegib）阻断该信号通路可以抑制肿瘤生长。表皮细胞中的初级纤毛在刺猬信号相关蛋白的加工中起着不可或缺的作用。最近的基因组研究指出，可能与基底细胞癌的发展有关的其他基因突变的参与，表明除了刺猬蛋白之外，其他信号通路（例如 WNT、NOTCH、mTOR 和 Hippo）在这种人类肿瘤的发病机制中也具有重要意义。其中一些途径可能受到非编码 microRNA 的调节。随着这些病变的进展，微小RNA表达谱的改变被识别出来。停止使用 Smoothened (SMO) 抑制剂治疗通常会导致基底细胞痣综合征患者的肿瘤复发，这些患者会出现 10-100 个基底细胞癌。此外，由于 SMO 药物结合域发生突变，这些 SMO 抑制剂的初始有效性受到损害。这些数据表明需要制定策略来克服肿瘤复发和耐药性，并通过开发新的基于单一药物或基于多种药物的组合方法来提高疗效。免疫疗法和光动力疗法可能是另外的成功方法，特别是如果与化疗联合开发用于无法手术和转移性基底细胞癌。
Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10–100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs.
登录
查看更多内容
影响因子：
5.6
作者：
Bertoli G;Cava C;Castiglioni I
通讯作者：
Castiglioni I
DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
影响因子：
11.5
作者：
Axelson, Michael;Liu, Ke;Pazdur, Richard
通讯作者：
Pazdur, Richard
影响因子：
2.4
作者：
Aftergut, K;Curry, M;Cohen, J
通讯作者：
Cohen, J
DOI：
10.1016/j.cub.2014.08.047
发表时间：
2014-10-06
期刊：
Current biology : CB
影响因子：
--
作者：
Brooks ER;Wallingford JB
通讯作者：
Wallingford JB