Nicolini Fabio, Bocchini Martine, Bronte Giuseppe, Delmonte Angelo, Guidoboni Massimo, Crinò Lucio, Mazza Massimiliano
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Front Oncol. 2020 Jan 24;9:1519. doi: 10.3389/fonc.2019.01519. eCollection 2019.
Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8-14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing. The exact molecular mechanisms that explain the carcinogenicity of asbestos are not known. Standard therapeutic strategies for MPM include surgery, often coupled with chemotherapy and/or radiotherapy, in a small percentage of eligible patients and chemotherapy in tumors considered unresectable with or without adjuvant radiotherapy. In recent years, several new therapeutic avenues are being explored. These include angiogenesis inhibitors, synthetic lethal treatment, miRNA replacement, oncoviral therapies, and the fast-growing field of immunotherapy alone or in combination with chemotherapy. Of particular promise are the multiple options offered by immunotherapy: immune checkpoint inhibitors, tumor vaccines, and therapies taking advantage of tumor-specific antigens, such as specific therapeutic antibodies or advanced cell-based therapies exemplified by the CAR-T cells. This review comprehensively presents both old and new therapeutic options in MPM, focusing on the results of the numerous recent and on-going clinical trials in the field, including the latest data presented at international meetings (AACR, ASCO, and ESMO) this year, and concludes that more work has to be done in the framework of tailored therapies to identify reliable targets and novel biomarkers to impact MPM management.
恶性胸膜间皮瘤(MPM)是一种与石棉暴露相关的罕见侵袭性胸膜表面癌症。MPM患者的中位生存期仅为8 - 14个月,几乎没有生物标志物,也没有治愈方法。鉴于大多数国家已禁止使用石棉,人们希望MPM的发病率最终会下降并保持在低水平且稳定,但与此同时,欧洲的发病率仍在上升。目前尚不清楚解释石棉致癌性的确切分子机制。MPM的标准治疗策略包括手术,在一小部分符合条件的患者中通常联合化疗和/或放疗,对于被认为不可切除的肿瘤,无论有无辅助放疗,均采用化疗。近年来,人们正在探索几种新的治疗途径。这些包括血管生成抑制剂、合成致死治疗、miRNA替代、肿瘤病毒疗法,以及快速发展的免疫治疗领域,免疫治疗可单独使用或与化疗联合使用。免疫治疗提供的多种选择尤其具有前景:免疫检查点抑制剂、肿瘤疫苗,以及利用肿瘤特异性抗原的疗法,如特异性治疗抗体或以CAR - T细胞为代表的先进细胞疗法。本综述全面介绍了MPM的新旧治疗选择,重点关注该领域众多近期和正在进行的临床试验结果,包括今年在国际会议(美国癌症研究协会、美国临床肿瘤学会和欧洲肿瘤内科学会)上公布的最新数据,并得出结论,在量身定制的治疗框架内,还需要做更多工作来确定可靠的靶点和新型生物标志物,以影响MPM的治疗管理。