Department of Melanoma, Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale Tumor IRCCS "Fondazione G. Pascale", Naples, Italy.
Hematology & Oncology, Temple University and Cancer Expert Now, Bethlehem, PA, USA.
J Transl Med. 2022 Sep 4;20(1):391. doi: 10.1186/s12967-022-03592-4.
Advances in immune checkpoint and combination therapy have led to improvement in overall survival for patients with advanced melanoma. Improved understanding of the tumor, tumor microenvironment and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. Combination modalities with other immunotherapy agents, chemotherapy, radiotherapy, electrochemotherapy are also being explored to overcome resistance and to potentiate the immune response. In addition, novel approaches such as adoptive cell therapy, oncogenic viruses, vaccines and different strategies of drug administration including sequential, or combination treatment are being tested. Despite the progress in diagnosis of melanocytic lesions, correct classification of patients, selection of appropriate adjuvant and systemic theràapies, and prediction of response to therapy remain real challenges in melanoma. Improved understanding of the tumor microenvironment, tumor immunity and response to therapy has prompted extensive translational and clinical research in melanoma. There is a growing evidence that genomic and immune features of pre-treatment tumor biopsies may correlate with response in patients with melanoma and other cancers, but they have yet to be fully characterized and implemented clinically. Development of novel biomarker platforms may help to improve diagnostics and predictive accuracy for selection of patients for specific treatment. Overall, the future research efforts in melanoma therapeutics and translational research should focus on several aspects including: (a) developing robust biomarkers to predict efficacy of therapeutic modalities to guide clinical decision-making and optimize treatment regimens, (b) identifying mechanisms of therapeutic resistance to immune checkpoint inhibitors that are potentially actionable, (c) identifying biomarkers to predict therapy-induced adverse events, and (d) studying mechanism of actions of therapeutic agents and developing algorithms to optimize combination treatments. During the Melanoma Bridge meeting (December 2nd-4th, 2021, Naples, Italy) discussions focused on the currently approved systemic and local therapies for advanced melanoma and discussed novel biomarker strategies and advances in precision medicine as well as the impact of COVID-19 pandemic on management of melanoma patients.
免疫检查点和联合治疗的进展改善了晚期黑色素瘤患者的总生存期。对肿瘤、肿瘤微环境和肿瘤免疫逃逸机制的深入了解,促使人们采用新的方法来靶向和利用宿主的免疫反应。还探索了联合其他免疫治疗药物、化疗、放疗、电化学疗法等方法,以克服耐药性并增强免疫反应。此外,还正在尝试采用新方法,如过继细胞疗法、致癌病毒、疫苗和不同的药物给药策略,包括序贯或联合治疗。
尽管在黑素细胞病变的诊断、正确分类患者、选择适当的辅助和系统治疗以及预测对治疗的反应方面取得了进展,但在黑色素瘤中仍然存在真正的挑战。对肿瘤微环境、肿瘤免疫和对治疗的反应的深入了解,促使人们在黑色素瘤中进行了广泛的转化和临床研究。越来越多的证据表明,治疗前肿瘤活检的基因组和免疫特征可能与黑色素瘤和其他癌症患者的反应相关,但尚未得到充分描述和临床应用。开发新的生物标志物平台可能有助于改善诊断和预测准确性,以便为特定治疗选择患者。
总之,黑色素瘤治疗和转化研究的未来研究工作应侧重于以下几个方面:(a)开发强大的生物标志物,以预测治疗方式的疗效,从而指导临床决策并优化治疗方案;(b)确定潜在可治疗的免疫检查点抑制剂治疗耐药机制;(c)确定预测治疗相关不良反应的生物标志物;(d)研究治疗药物的作用机制,并开发算法来优化联合治疗。
在黑色素瘤桥接会议(2021 年 12 月 2 日至 4 日,意大利那不勒斯)上,讨论集中在目前批准的晚期黑色素瘤的全身和局部治疗方法上,并讨论了新型生物标志物策略和精准医学的进展,以及 COVID-19 大流行对黑色素瘤患者管理的影响。