New insights on the role of autophagy in the pathogenesis and treatment of melanoma
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REVIEW
New insights on the role of autophagy in the pathogenesis and treatment of melanoma Marveh Rahmati1 · Shiva Ebrahim2 · Saadeh Hashemi1 · Masoumeh Motamedi1 · Mohammad Amin Moosavi3 Received: 21 May 2020 / Accepted: 30 September 2020 © Springer Nature B.V. 2020
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. Keywords Autophagy · Drug resistance · Melanoma · Skin cancer · Therapy
Introduction The skin is composed of two main layers: (i) the epidermis, the outer layer that mostly consist of keratinocytes and (ii) the dermis, which contains fibroblasts, mast cells, * Marveh Rahmati [email protected] * Mohammad Amin Moosavi a‑[email protected] Shiva Ebrahim [email protected] Saadeh Hashemi [email protected] Masoumeh Motamedi [email protected] 1
Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran
2
Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
3
Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, P.O. Box14965/161, Tehran, Iran
macrophages and Langerhans’ cells. Melanocytes reside along the basal layer of the epidermis and their main function is to provide and deliver melanin to keratinocytes, leading to the skin pigmentation and its protection against ultraviolet (UV) damage [1]. Skin cancer is the most common form of cancers in the United States, which represents 40–50% of all diagnosed cancers [2], and broadly classified into two types: nonmelanoma skin cancers (NMSCs) and melanoma [3]. Although melanoma accounts for about 1–4% of all skin cancers, it is the most aggressive and lethal form with approximately 60% mortality rates [2]. It has been well evidenced that somatic mutations
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