Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
Section of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
Sci Rep. 2022 Jun 15;12(1):9951. doi: 10.1038/s41598-022-14197-8.
Adenoid cystic carcinoma (ACC) is a rare malignancy characterized by high incidence of relapse. When relapsing, ACC has an indolent but relentless behaviour, thus leading to a poor long-term prognosis. The treatment of choice of relapsing ACC remains surgery followed by radiotherapy, whenever feasible. Therapeutic weapons are limited to systemic drugs. The most widely used chemotherapy regimen is the combination of cisplatin and doxorubicin, however with low response rate and not long lasting; there is also a lack of alternatives for second line therapies in case of disease progression. Therefore, a more comprehensive strategy aimed at identifying at preclinical level the most promising drugs or combination is clearly needed. In this study, the cytotoxic effects of two standard chemotherapy drugs, cisplatin and doxorubicin, and of five targeted therapy-drugs was tested in vitro, on an h-TERT immortalized ACC cell line, and in vivo, on zebrafish embryos with ACC tumoral cell xenograft. Then, combinations of one standard chemotherapy drug plus one targeted therapy drug were also evaluated, in order to find the best treatment strategy for ACC. Data obtained demonstrated that both vorinostat and olaparib significantly increased the standard chemotherapy cytotoxic effects, suggesting new interesting therapeutic options for ACC.
腺样囊性癌 (ACC) 是一种罕见的恶性肿瘤，其复发率很高。当复发时，ACC 具有惰性但无情的行为，因此导致预后不良。复发性 ACC 的治疗选择仍然是手术加放疗，如果可行的话。治疗手段仅限于全身药物。最广泛使用的化疗方案是顺铂和多柔比星的联合用药，但反应率低且持续时间不长；如果疾病进展，二线治疗也缺乏替代药物。因此，显然需要制定更全面的策略，旨在在临床前水平上确定最有前途的药物或联合用药。在这项研究中，两种标准化疗药物顺铂和多柔比星，以及五种靶向治疗药物在体外对 h-TERT 永生化 ACC 细胞系进行了细胞毒性测试，并在携带 ACC 肿瘤细胞异种移植物的斑马鱼胚胎中进行了体内测试。然后，还评估了一种标准化疗药物加一种靶向治疗药物的联合用药，以找到治疗 ACC 的最佳治疗策略。获得的数据表明，伏立诺他和顺铂联合使用显著增加了标准化疗的细胞毒性作用，这为 ACC 提供了新的有前途的治疗选择。
