Catalani Elisabetta, Giovarelli Matteo, Zecchini Silvia, Perrotta Cristiana, Cervia Davide
Department for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, Largo dell'Università snc, 01100 Viterbo, Italy.
Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Università degli Studi di Milano, Via G.B. Grassi 74, 20157 Milano, Italy.
Cancers (Basel). 2021 Nov 18;13(22):5791. doi: 10.3390/cancers13225791.
Melanoma originates from the malignant transformation of melanocytes and is one of the most aggressive forms of cancer. The recent approval of several drugs has increased the chance of survival although a significant subset of patients with metastatic melanoma do not show a long-lasting response to these treatments. The complex cross-talk between oxidative stress and the catabolic process autophagy seems to play a central role in all aspects of melanoma pathophysiology, from initiation to progression and metastasis, including drug resistance. However, determining the fine role of autophagy in cancer death and in response to redox disruption is still a fundamental challenge in order to advance both basic and translational aspects of this field. In order to summarize the interactions among reactive oxygen and nitrogen species, autophagy machinery and proliferation/growth/death/apoptosis/survival, we provide here a narrative review of the preclinical evidence for drugs/treatments that modulate oxidative stress and autophagy in melanoma cells. The significance and the potential for pharmacological targeting (also through multiple and combination approaches) of these two different events, which can contribute independently or simultaneously to the fate of melanoma, may help to define new processes and their interconnections underlying skin cancer biology and unravel new reliable approaches.
黑色素瘤起源于黑素细胞的恶性转化，是最具侵袭性的癌症形式之一。尽管有几种药物最近获批，提高了患者的生存几率，但相当一部分转移性黑色素瘤患者对这些治疗并未表现出持久反应。氧化应激与分解代谢过程自噬之间复杂的相互作用似乎在黑色素瘤病理生理学的各个方面都起着核心作用，从起始到进展和转移，包括耐药性。然而，确定自噬在癌症死亡及对氧化还原破坏的反应中的具体作用，仍然是推进该领域基础和转化研究的一项根本性挑战。为了总结活性氧和氮物种、自噬机制与增殖/生长/死亡/凋亡/存活之间的相互作用，我们在此对调节黑色素瘤细胞中氧化应激和自噬的药物/治疗的临床前证据进行叙述性综述。这两种不同事件（可独立或同时影响黑色素瘤的转归）的药理学靶向（包括通过多种和联合方法）的意义及潜力，可能有助于明确皮肤癌生物学背后的新过程及其相互联系，并揭示新的可靠方法。
