摘要
Melanoma is the most lethal skin cancer that originates from the malignant transformation of melanocytes.Although melanoma has long bee n regarded as a cancerous malig nancy with few therapeutic opti ons,in creased biological understandi ng and unprecedented innovations in therapies targeting mutated driver genes and immune checkpoints have substantially improved the prog nosis of patients.However,the low response rate and inevitable occurre nee of resistance to curre ntly available targeted therapies have posed the obstacle in the path of melanoma management to obtain further amelioration.Therefore,it is necessary to understand the mechanisms underlying melanoma pathogenesis more comprehensively,which might lead to more substantial progress in therapeutic approaches and expand clinical options for melanoma therapy.In this review,we firstly make a brief introduction to melanoma epidemiology,clinical subtypes,risk factors,and current therapies.Then,the signal pathways orchestrati ng mela noma pathogenesis,in eluding gen etic mutatio ns,key tran scripti onal regulators,epige netic dysregulati ons,metabolic reprogramming,crucial metastasis-related signals,tumor-promoting inflammatory pathways,and pro-angiogenic factors,have been systemically reviewed and discussed.Subsequently,we outline current progresses in therapies targeting mutated driver genes and immune checkpoi nts,as well as the mecha nisms underlying the treatment resista nee.Finally,the prospects and challe nges in the developme nt of mela noma therapy,especially immu no therapy and related ongoing din ical trials,are summarized and discussed.
基金
This work has received funding from the National Natural Science Foundation of China(Nos.81625020,81902791)
Support Program of Young Talents in Shaanxi Province(No.20200303)
Young Eagle Project of Fourth Military Medical University(No.2019cyjhgwn).
