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自噬在黑色素瘤发病机制和治疗中的作用的新见解。

New insights on the role of autophagy in the pathogenesis and treatment of melanoma.

作者信息

Rahmati Marveh, Ebrahim Shiva, Hashemi Saadeh, Motamedi Masoumeh, Moosavi Mohammad Amin

机构信息

Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.

出版信息

Mol Biol Rep. 2020 Nov;47(11):9021-9032. doi: 10.1007/s11033-020-05886-6. Epub 2020 Oct 9.

Abstract

Despite the depth of knowledge concerning the pathogenesis of melanoma, the most aggressive type of skin cancer, the prognosis and survival of patients still remain a challenge. In addition, responses to chemotherapy and immunotherapy are still poor, which underscore an urgent need in the development of new therapeutic strategies for the treatment of melanoma. Recently, the dynamic role of autophagy has gained considerable interest in the pathogenesis and treatment of melanoma. Whereas a decrease in autophagy activity promotes melanoma formation by increasing oncogene-induced tumorigenesis and DNA damage accumulation, an enhanced level of autophagy sustains melanoma cell viability and contributes to drug resistance. Obviously, the understanding of autophagy regulation may lead to a better defining melanoma pathogenesis and the progression toward new treatment options. In this review, we present new insights into a dual role of autophagy during melanoma tumorigenesis. In addition to summarizing current therapeutics for treating melanoma, we discuss how autophagy manipulation may improve the patients' outcome. Finally, autophagy-modulating drugs and nanoparticles, alone or in combination with current therapeutics, are proposed for possible clinical use in melanoma management.

摘要

尽管对黑色素瘤(最具侵袭性的皮肤癌类型)的发病机制已有深入了解,但患者的预后和生存率仍然是一项挑战。此外,化疗和免疫疗法的反应仍然不佳,这凸显了开发治疗黑色素瘤新治疗策略的迫切需求。最近,自噬的动态作用在黑色素瘤的发病机制和治疗中引起了相当大的关注。自噬活性降低通过增加致癌基因诱导的肿瘤发生和DNA损伤积累促进黑色素瘤形成,而自噬水平增强则维持黑色素瘤细胞活力并导致耐药性。显然,对自噬调节的理解可能有助于更好地界定黑色素瘤的发病机制以及向新治疗选择的进展。在本综述中,我们展示了对自噬在黑色素瘤肿瘤发生过程中的双重作用的新见解。除了总结目前治疗黑色素瘤的疗法外,我们还讨论了自噬调控如何改善患者的预后。最后,提出了自噬调节药物和纳米颗粒,单独或与目前的疗法联合使用,可能用于黑色素瘤治疗的临床应用。

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