Falcone Italia, Conciatori Fabiana, Bazzichetto Chiara, Ferretti Gianluigi, Cognetti Francesco, Ciuffreda Ludovica, Milella Michele
Medical Oncology, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy.
SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy.
Cancers (Basel). 2020 Oct 6;12(10):2870. doi: 10.3390/cancers12102870.
Antitumor therapies have made great strides in recent decades. Chemotherapy, aggressive and unable to discriminate cancer from healthy cells, has given way to personalized treatments that, recognizing and blocking specific molecular targets, have paved the way for targeted and effective therapies. Melanoma was one of the first tumor types to benefit from this new care frontier by introducing specific inhibitors for v-Raf murine sarcoma viral oncogene homolog B (BRAF), mitogen-activated protein kinase (MEK), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and, recently, immunotherapy. However, despite the progress made in the melanoma treatment, primary and/or acquired drug resistance remains an unresolved problem. The molecular dynamics that promote this phenomenon are very complex but several studies have shown that the tumor microenvironment (TME) plays, certainly, a key role. In this review, we will describe the new melanoma treatment approaches and we will analyze the mechanisms by which TME promotes resistance to targeted therapy and immunotherapy.
近几十年来，抗肿瘤治疗取得了巨大进展。化疗具有侵袭性且无法区分癌细胞和健康细胞，如今已被个性化治疗所取代。个性化治疗能够识别并阻断特定分子靶点，为靶向有效治疗铺平了道路。黑色素瘤是最早受益于这一新型治疗前沿领域的肿瘤类型之一，通过引入针对v-Raf鼠肉瘤病毒癌基因同源物B（BRAF）、丝裂原活化蛋白激酶（MEK）、v-kit哈迪-朱克曼4型猫肉瘤病毒癌基因同源物（KIT）的特异性抑制剂，以及最近的免疫疗法。然而，尽管黑色素瘤治疗取得了进展，但原发性和/或获得性耐药仍然是一个未解决的问题。促成这一现象的分子动力学非常复杂，但多项研究表明，肿瘤微环境（TME）无疑起着关键作用。在本综述中，我们将描述黑色素瘤的新型治疗方法，并分析肿瘤微环境促进对靶向治疗和免疫治疗耐药的机制。
