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维莫德吉和索尼德吉治疗局部晚期和转移性基底细胞癌: hedgehog 通路抑制剂的最新进展。

Vismodegib and Sonidegib in Locally Advanced and Metastatic Basal Cell Carcinoma: Update on Hedgehog Pathway Inhibitors.

机构信息

Servicio de Dermatología y Venerología, Facultad de Medicina, Universidad Hasanuddin, Makassar, Indonesia.

Servicio de Dermatología y Venerología, Facultad de Medicina, Universidad Hasanuddin, Makassar, Indonesia.

出版信息

Actas Dermosifiliogr. 2022 May;113(5):443-450. doi: 10.1016/j.ad.2022.01.005. Epub 2022 Jan 31.

Abstract

As one of the most common malignancies, basal cell carcinoma (BCC) has evolved as a global burden with incidence annually rising, especially in the older population. Even though the condition is mostly localized, the nature of the disease is destructive and can evolve as either locally advanced BCC (laBCC) or even more rarely as metastatic BCC (mBCC). There are well-established conventional treatment options for these cases, including surgeries and radiotherapy. However, not all cases are eligible for conventional treatments. Recently, biologic treatment has gained a lot of attention and research. This has led to the development of targeted treatment involving the hedgehog pathway inhibitor (HPI), a key pathogenesis in laBCC and mBCC. There are currently two approved HPIs, vismodegib and sonidegib to treat inoperable laBCC and mBCC. This review seeks to explore the pathophysiology of hedgehog pathway behind the development of BCC, and the current update of the efficacy as well as pharmacokinetics properties of HPIs that led to the ideal treatment for laBCC or mBCC, either as monotherapy or in combination with other conventional therapies.

摘要

作为最常见的恶性肿瘤之一,基底细胞癌(BCC)已成为一种全球性负担,其发病率呈逐年上升趋势,尤其是在老年人群中。尽管这种疾病大多局限于局部,但它具有破坏性,可能发展为局部晚期基底细胞癌(laBCC),甚至更罕见的转移基底细胞癌(mBCC)。对于这些病例,有成熟的常规治疗方案,包括手术和放疗。然而,并非所有病例都适合常规治疗。最近,生物治疗引起了广泛关注和研究。这导致了针对涉及 hedgehog 通路抑制剂(HPI)的靶向治疗的发展,HPI 是 laBCC 和 mBCC 的关键发病机制。目前有两种批准的 HPI,vismodegib 和 sonidegib,用于治疗不可手术的 laBCC 和 mBCC。本综述旨在探讨 BCC 发展背后 hedgehog 通路的病理生理学,以及 HPI 的疗效和药代动力学特性的最新进展,这些进展导致了 laBCC 或 mBCC 的理想治疗方法,无论是单独使用还是与其他常规疗法联合使用。

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