中华皮肤科杂志 ›› 2021, Vol. 54 ›› Issue (1): 27-32.doi: 10.35541/cjd.20200560
高天文 郭伟楠
收稿日期:
2020-06-08
修回日期:
2020-11-12
发布日期:
2021-01-05
通讯作者:
高天文
E-mail:gaotw75401@163.com
Gao Tianwen, Guo Weinan
Received:
2020-06-08
Revised:
2020-11-12
Published:
2021-01-05
Contact:
Gao Tianwen
E-mail:gaotw75401@163.com
摘要: 【摘要】 尽管黑素瘤发病率正快速增长,但其在中国所占比例低,肿瘤科医生关注少。黑素瘤患者首诊科室主要是皮肤科,皮肤科医生能综合分析临床诊断、病理诊断、外科治疗和药物治疗,对黑素瘤的诊治具有独特优势。中国学者近年在黑素瘤的细胞死亡调控、表观遗传学修饰、靶向药物耐药、肿瘤微环境和肿瘤免疫调控等方面已获得很大进展。中国独有的一类新药干扰素α-1b不仅可用于Ⅱ、Ⅲ期高危黑素瘤的辅助治疗,对Ⅳ期黑素瘤也有很好的疗效,不良反应远低于干扰素α-2b。与白色人种不同,亚洲人皮肤黑素瘤以肢端型及黏膜型为主。以干扰素α-1b为基础制定联合治疗策略,探索其与程序性死亡受体-配体1抑制剂、靶向药物或血管生成抑制剂等的联合治疗方案,正在为挽救Ⅳ期黑素瘤患者带来希望。
高天文 郭伟楠. 中国黑素瘤研究进展与新治疗策略[J]. 中华皮肤科杂志, 2021,54(1):27-32. doi:10.35541/cjd.20200560
Gao Tianwen, Guo Weinan. Research progress in and new treatment strategies for melanoma in China[J]. Chinese Journal of Dermatology, 2021, 54(1): 27-32.doi:10.35541/cjd.20200560
[1] | Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: evidence⁃based changes in the American Joint Committee on Cancer eighth edition cancer staging manual[J]. CA Cancer J Clin, 2017,67(6):472⁃492. doi: 10.3322/caac.21409. |
[2] | Mocellin S, Pasquali S, Rossi CR, et al. Interferon alpha adjuvant therapy in patients with high⁃risk melanoma: a systematic review and meta⁃analysis[J]. J Natl Cancer Inst,2010,102(7):493⁃501. doi: 10.1093/jnci/djq009. |
[3] | Hodi FS, O′Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma[J]. N Engl J Med, 2010,363(8):711⁃723. doi: 10.1056/NEJMoa100 3466. |
[4] | Robert C, Ribas A, Schachter J, et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE⁃006): post⁃hoc 5⁃year results from an open⁃label, multicentre, randomised, controlled, phase 3 study[J]. Lancet Oncol, 2019,20(9):1239⁃1251. doi: 10.1016/S1470⁃2045(19)30388⁃2. |
[5] | Eggermont A, Blank CU, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma[J]. N Engl J Med, 2018,378(19):1789⁃1801. doi: 10.1056/NEJMoa1802357. |
[6] | Larkin J, Chiarion⁃Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma[J]. N Engl J Med,2015,373(1):23⁃34. doi: 10.1056/NEJMoa1504030. |
[7] | Robert C, Grob JJ, Stroyakovskiy D, et al. Five⁃year outcomes with dabrafenib plus trametinib in metastatic melanoma[J]. N Engl J Med, 2019,381(7):626⁃636. doi: 10.1056/NEJMoa1904 059. |
[8] | Erkes DA, Cai W, Sanchez IM, et al. Mutant BRAF and MEK inhibitors regulate the tumor immune microenvironment via pyroptosis[J]. Cancer Discov, 2020,10(2):254⁃269. doi: 10.1158/ 2159⁃8290.CD⁃19⁃0672. |
[9] | Schilling B, Martens A, Geukes Foppen MH, et al. First⁃line therapy⁃stratified survival in BRAF⁃mutant melanoma: a retrospective multicenter analysis[J]. Cancer Immunol Immunother, 2019,68(5):765⁃772. doi: 10.1007/s00262⁃019⁃02311⁃1. |
[10] | Curtin JA, Busam K, Pinkel D, et al. Somatic activation of KIT in distinct subtypes of melanoma[J]. J Clin Oncol, 2006,24(26):4340⁃4346. doi: 10.1200/JCO.2006.06.2984. |
[11] | Guo J, Carvajal RD, Dummer R, et al. Efficacy and safety of nilotinib in patients with KIT⁃mutated metastatic or inoperable melanoma: final results from the global, single⁃arm, phase II TEAM trial[J]. Ann Oncol, 2017,28(6):1380⁃1387. doi: 10. 1093/annonc/mdx079. |
[12] | Bai X, Kong Y, Chi Z,et al. MAPK pathway and TERT promoter gene mutation pattern and its prognostic value in melanoma patients: a retrospective study of 2,793 cases[J]. Clin Cancer Res,2017,23(20):6120⁃6127. doi: 10.1158/1078⁃0432.CCR⁃17⁃0980. |
[13] | Ascierto PA, Schadendorf D, Berking C, et al. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non⁃randomised, open⁃label phase 2 study[J]. Lancet Oncol, 2013,14(3):249⁃256. doi: 10.1016/S1470⁃2045(13)70024⁃X. |
[14] | Li J, Huang Q, Long X, et al. Mitochondrial elongation⁃mediated glucose metabolism reprogramming is essential for tumour cell survival during energy stress[J]. Oncogene, 2017,36(34):4901⁃4912. doi: 10.1038/onc.2017.98. |
[15] | Li XX, Wang ZJ, Zheng Y, et al. Nuclear receptor Nur77 facilitates melanoma cell survival under metabolic stress by protecting fatty acid oxidation[J]. Mol Cell, 2018,69(3):480⁃492.e7. doi: 10.1016/j.molcel.2018.01.001. |
[16] | Zhou B, Zhang JY, Liu XS, et al. Tom20 senses iron⁃activated ROS signaling to promote melanoma cell pyroptosis[J]. Cell Res, 2018,28(12):1171⁃1185. doi: 10.1038/s41422⁃018⁃0090⁃y. |
[17] | Yang Y, Luo M, Zhang K, et al. Nedd4 ubiquitylates VDAC2/3 to suppress erastin⁃induced ferroptosis in melanoma[J]. Nat Commun, 2020,11(1):433. doi: 10.1038/s41467⁃020⁃14324⁃x. |
[18] | Guo W, Wang H, Yang Y, et al. Down⁃regulated miR⁃23a contributes to the metastasis of cutaneous melanoma by promoting autophagy[J]. Theranostics, 2017,7(8):2231⁃2249. doi: 10.7150/thno.18835. |
[19] | Ma M, Dai J, Tang H, et al. MicroRNA⁃23a⁃3p inhibits mucosal melanoma growth and progression through targeting adenylate cyclase 1 and attenuating cAMP and MAPK pathways[J]. Theranostics, 2019,9(4):945⁃960. doi: 10.7150/thno.30516. |
[20] | Wang L, Guo W, Ma J, et al. Aberrant SIRT6 expression contributes to melanoma growth: role of the autophagy paradox and IGF⁃AKT signaling[J]. Autophagy, 2018,14(3):518⁃533. doi: 10.1080/15548627.2017.1384886. |
[21] | Guo W, Ma J, Yang Y, et al. ATP⁃citrate lyase epigenetically potentiates oxidative phosphorylation to promote melanoma growth and adaptive resistance to MAPK inhibition[J]. Clin Cancer Res, 2020,26(11):2725⁃2739. doi: 10.1158/1078⁃0432.CCR⁃19⁃1359. |
[22] | Manzano JL, Layos L, Bugés C, et al. Resistant mechanisms to BRAF inhibitors in melanoma[J]. Ann Transl Med, 2016,4(12):237. doi: 10.21037/atm.2016.06.07. |
[23] | Han S, Ren Y, He W, et al. ERK⁃mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma[J]. Nat Commun, 2018,9(1):28. doi: 10.1038/ s41467⁃017⁃02354⁃x. |
[24] | Kong Y, Sheng X, Wu X, et al. Frequent genetic aberrations in the CDK4 pathway in acral melanoma indicate the potential for CDK4/6 inhibitors in targeted therapy[J]. Clin Cancer Res, 2017,23(22):6946⁃6957. doi: 10.1158/1078⁃0432.CCR⁃17⁃0070. |
[25] | Kong Y, Si L, Li Y, et al. Analysis of mTOR gene aberrations in melanoma patients and evaluation of their sensitivity to PI3K⁃AKT⁃mTOR pathway inhibitors[J]. Clin Cancer Res, 2016,22(4):1018⁃1027. doi: 10.1158/1078⁃0432.CCR⁃15⁃1110. |
[26] | Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade[J]. Science, 2018,359(6382):1350⁃1355. doi: 10.1126/ science.aar4060. |
[27] | Meng X, Liu X, Guo X, et al. FBXO38 mediates PD⁃1 ubiquitination and regulates anti⁃tumour immunity of T cells[J]. Nature, 2018,564(7734):130⁃135. doi: 10.1038/s41586⁃018⁃0756⁃0. |
[28] | Ma X, Bi E, Huang C, et al. Cholesterol negatively regulates IL⁃9⁃producing CD8+ T cell differentiation and antitumor activity[J]. J Exp Med, 2018,215(6):1555⁃1569. doi: 10.1084/jem.20171576. |
[29] | Liu H, Kuang X, Zhang Y, et al. ADORA1 inhibition promotes tumor immune evasion by regulating the ATF3⁃PD⁃L1 axis[J]. Cancer Cell, 2020,37(3):324⁃339.e8. doi: 10.1016/j.ccell. 2020.02.006. |
[30] | Huang L, Li Y, Du Y, et al. Mild photothermal therapy potentiates anti⁃PD⁃L1 treatment for immunologically cold tumors via an all⁃in⁃one and all⁃in⁃control strategy[J]. Nat Commun, 2019,10(1):4871. doi: 10.1038/s41467⁃019⁃12771⁃9. |
[31] | Xu YP, Lv L, Liu Y, et al. Tumor suppressor TET2 promotes cancer immunity and immunotherapy efficacy[J]. J Clin Invest, 2019,129(10):4316⁃4331. doi: 10.1172/JCI129317. |
[32] | Yu J, Yan J, Guo Q, et al. Genetic aberrations in the CDK4 pathway are associated with innate resistance to PD⁃1 blockade in Chinese patients with non⁃cutaneous melanoma[J]. Clin Cancer Res, 2019,25(21):6511⁃6523. doi: 10.1158/1078⁃0432.CCR⁃19⁃0475. |
[33] | Sheng X, Yan X, Chi Z, et al. Axitinib in combination with toripalimab, a humanized immunoglobulin G4 monoclonal antibody against programmed cell death⁃1, in patients with metastatic mucosal melanoma: an open⁃label phase IB trial[J]. J Clin Oncol, 2019,37(32):2987⁃2999. doi: 10.1200/JCO.19.00210. |
[34] | Zhang Q, Bi J, Zheng X, et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti⁃tumor immunity[J]. Nat Immunol, 2018,19(7):723⁃732. doi: 10.1038/s41590⁃018⁃0132⁃0. |
[35] | Yang M, Chen S, Du J, et al. NK cell development requires Tsc1⁃dependent negative regulation of IL⁃15⁃triggered mTORC1 activation[J]. Nat Commun, 2016,7:12730. doi: 10.1038/ncomms 12730. |
[36] | Yu X, Lao Y, Teng XL, et al. SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation[J]. Nat Commun, 2018,9(1):3157. doi: 10.1038/s41467⁃018⁃05676⁃6. |
[37] | Si L, Zhang X, Shu Y, et al. A phase Ib study of pembrolizumab as second⁃line therapy for Chinese patients with advanced or metastatic melanoma (KEYNOTE⁃151)[J]. Transl Oncol, 2019,12(6):828⁃835. doi: 10.1016/j.tranon.2019.02.007. |
[38] | Liu Y, Ma J, Yang Y, et al. Impact of interferon⁃alpha1b (IFN⁃α1b) on antitumor immune response: an interpretation of the promising therapeutic effect of IFN⁃alpha1b on melanoma[J]. Med Sci Monit, 2020,26:e922790. doi: 10.12659/MSM.922790. |
[1] | 张宁, 李舒, 李敬. 免疫检查点抑制剂和靶向药物辅助治疗可切除黑素瘤疗效的网状Meta分析[J]. 中华皮肤科杂志, 2022, 0(4): 20200767-e20200767. |
[2] | 李妍 李明 徐薇 李邻峰. 【开放获取】丙酸氟替卡松乳膏单独或联合卡泊三醇软膏治疗轻中度斑块状银屑病的随机自身对照研究[J]. 中华皮肤科杂志, 2022, 55(3): 260-263. |
[3] | 李浩, 王俐 韩宪伟 孙彤 苏芳 孙晓冬 韩莹 杨国玲 刘晓明 王凯波 . 糖尿病患者服用二肽基肽酶Ⅳ抑制剂后发生大疱性类天疱疮32例临床特征分析[J]. 中华皮肤科杂志, 2022, 55(3): 213-218. |
[4] | 《脓疱型银屑病诊疗中国专家共识(版)》编写委员会专家组. 脓疱型银屑病诊疗中国专家共识(2022版)[J]. 中华皮肤科杂志, 2022, 55(3): 187-195. |
[5] | 王娟娟 陈容 季江 苏文星 魏钰倩 赵莹 尹兴平 苏玉华 施辛. 以精神行为异常为首发症状的67例神经梅毒患者回顾性分析[J]. 中华皮肤科杂志, 2022, 55(3): 231-234. |
[6] | 温广东 冒丹丹 张原媛 窦沅青 赵培 吴晨雨 张建中. 【开放获取】度普利尤单抗治疗泛发性苔藓状淀粉样变1例国内首报[J]. 中华皮肤科杂志, 2022, 0(2): 20210694-e20210694. |
[7] | 李赛, 薛华忠, 张树文, 蒋娟, 齐淑贞, 赵园园, 张津萍, 沙仲, 乐文静, 王碧伟, 赵诗轩, 朱小凤, 苏晓红. 多西环素-莫西沙星序贯疗法治疗生殖支原体尿道炎/宫颈炎的临床观察[J]. 中华皮肤科杂志, 2022, 0(2): 20210631-e20210631. |
[8] | 高妮, 刘宇, 王雷, 刘玲, 高天文, 李凯. 孤立性真皮黑素瘤5例临床及组织病理分析[J]. 中华皮肤科杂志, 2022, 0(2): 20200775-e20200775. |
[9] | 焦晓燕, 尹光文, 阴亚坤, 李冬芹. 妊娠期、围生期带状疱疹25例临床分析[J]. 中华皮肤科杂志, 2022, 0(2): 20210384-e20210384. |
[10] | 王佳绮, 王平, 李刘雨, 樊奇敏, 朱蒙燕, 王燕清, 周鸿宇, 沈宏, 许爱娥. 皮肤色素减退性淋巴增殖性疾病41例临床病理分析[J]. 中华皮肤科杂志, 2022, 55(2): 110-115. |
[11] | 欧敏, 颜韵灵, 郑宝庆, 王晓华. 银屑病与肥胖相关性的研究进展[J]. 中华皮肤科杂志, 2022, 55(2): 181-184. |
[12] | 包诗杰, 程杨, 晏莹, 范昉, 高婷婷, 冯小兰, 郑亮, 雷卫, 黄琴斯, 张伟明, 周小勇. 人免疫球蛋白和重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗中毒性表皮坏死松解症的对比研究[J]. 中华皮肤科杂志, 2022, 55(2): 153-156. |
[13] | 郭静 杨景煜 丁黎 刘明明 侯晶梅 蒲小霞 孙嘉昱 李向花. 长脉宽1 064 nm Nd:YAG激光联合含滇山茶和三七等提取物的外用乳剂治疗黄褐斑的疗效[J]. 中华皮肤科杂志, 2022, 55(1): 61-64. |
[14] | 中华医学会皮肤性病学分会 中国医师协会皮肤科医师分会. 自身免疫性表皮下大疱病诊疗共识(2022)[J]. 中华皮肤科杂志, 2022, 55(1): 1-11. |
[15] | 董栋, 刘天一. 细胞代谢与皮肤恶性黑素瘤转移的研究进展[J]. 中华皮肤科杂志, 2022, 0(1): 20210023-e20210023. |
|