Troiani Teresa, Napolitano Stefania, Brancaccio Gabriella, Belli Valentina, Nappi Annarita, Miro Caterina, Salvatore Domenico, Dentice Monica, Caraglia Michele, Franco Renato, Giunta Emilio Francesco, De Falco Vincenzo, Ciardiello Davide, Ciardiello Fortunato, Argenziano Giuseppe
Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80131 Naples, Italy.
Dermatology Unit, Department of Mental and Physical Health and Prevention Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80131 Naples, Italy.
J Pers Med. 2021 Mar 14;11(3):206. doi: 10.3390/jpm11030206.
Melanoma is the most lethal form of skin cancer and its incidence is growing worldwide. In the last ten years, the therapeutic scenario of this disease has been revolutionized by the introduction of targeted therapies and immune-checkpoint inhibitors. However, in patients with many lesions and bulky tumors, in which surgery is no longer feasible, there is a need for new treatment options. Here we report, for the first time to our knowledge, a clinical case where a melanoma patient harboring the SMO p.Gln216Arg mutation has been treated with imiquimod, showing a complete and durable response. To better explain this outstanding response to the treatment, we transfected a melanoma cell line (MeWo) with the SMO p.Gln216Arg mutation in order to evaluate its role in response to the imiquimod treatment. Moreover, to better demonstrate that the antitumor activity of imiquimod was due to its role in suppressing the oncogenic SMO signaling pathway, independently of its immune modulating function, an in vivo experiment has been performed. This clinical case opens up a new scenario for the treatment of melanoma patients identifying a new potentially druggable target.
黑色素瘤是皮肤癌中最致命的一种，其发病率在全球范围内呈上升趋势。在过去十年中，靶向治疗和免疫检查点抑制剂的引入彻底改变了这种疾病的治疗模式。然而，对于有许多病灶和巨大肿瘤且手术不再可行的患者，需要新的治疗选择。据我们所知，我们首次报告了一例携带SMO p.Gln216Arg突变的黑色素瘤患者接受咪喹莫特治疗后出现完全且持久缓解的临床病例。为了更好地解释这种对治疗的显著反应，我们用SMO p.Gln216Arg突变转染了一种黑色素瘤细胞系（MeWo），以评估其在对咪喹莫特治疗反应中的作用。此外，为了更好地证明咪喹莫特的抗肿瘤活性是由于其在抑制致癌性SMO信号通路中的作用，而与其免疫调节功能无关，我们进行了一项体内实验。该临床病例为黑色素瘤患者的治疗开辟了新的前景，确定了一个新的潜在可药物靶向。
