Johannes Gutenberg University, Institute of Pharmaceutical and Biomedical Sciences, Mainz, Germany.
Department of Pharmacognosy, University of Khartoum, Khartoum, Sudan.
Cancer Genomics Proteomics. 2022 Jul-Aug;19(4):512-525. doi: 10.21873/cgp.20337.
Small cell vaginal carcinoma is a very rare gynecological cancer and treatments including chemo- and radiotherapy have had limited success.
We report the case of a 37-year-old female, where intensive treatment with the combination of paclitaxel, carboplatin, irinotecan, and camptothecin with and without irradiation did not avoid metastasis of the tumor and the death of the patient. In an attempt to develop a strategy for individualized tumor therapy, we performed immunohistochemistry of 19 cancer-related proteins using a biopsy sample. Strong expression was observed for glutathione S-transferase P1 (GSTP1), epidermal growth factor receptor (EGFR), inducible nitric oxide synthetase (iNOS), nuclear factor kappa B (NF-κB), the oncogene c-MYC, vascular endothelial growth factor (VEGF), and the proliferation marker Ki-67. Intermediate expression was found for the oncogene SRC, β-catenin, and the viral E7 protein. We then performed virtual drug screening with PyRx and molecular docking with AutoDock 4.2.6 by using the three-dimensional structures of these proteins and a chemical library of 1,577 FDA-approved drugs, in a drug repurposing approach. The top 15 compounds were either approved anticancer drugs or drugs used to treat non-malignant diseases. These compounds were bound with comparable or even higher affinity to the targets compared to control inhibitors. Several of these compounds were bound with high affinity to more than one of these target proteins, further supporting the drug repurposing concept.
These drugs might offer additional opportunities to reach treatment responses. This approach of individualized tumor therapy might be theoretically not only applicable for small cell vaginal carcinoma but for other tumor entities as well.
小细胞阴道癌是一种非常罕见的妇科癌症，包括化疗和放疗在内的治疗方法收效甚微。
我们报告了一例 37 岁女性的病例，她接受了紫杉醇、卡铂、伊立替康和喜树碱联合化疗，以及放化疗，但未能避免肿瘤转移和患者死亡。为了制定个体化肿瘤治疗策略，我们对活检样本进行了 19 种癌症相关蛋白的免疫组化分析。结果显示，谷胱甘肽 S-转移酶 P1（GSTP1）、表皮生长因子受体（EGFR）、诱导型一氧化氮合酶（iNOS）、核因子 kappa B（NF-κB）、癌基因 c-MYC、血管内皮生长因子（VEGF）和增殖标志物 Ki-67 表达较强。癌基因 SRC、β-连环蛋白和病毒 E7 蛋白表达为中等水平。然后，我们使用这些蛋白的三维结构和包含 1577 种 FDA 批准药物的化学库，通过 PyRx 进行虚拟药物筛选，并使用 AutoDock 4.2.6 进行分子对接，采用药物再利用方法进行研究。排名前 15 的化合物均为已批准的抗癌药物或用于治疗非恶性疾病的药物。与对照抑制剂相比，这些化合物与靶标的结合亲和力相当或更高。其中一些化合物与多个靶蛋白具有高亲和力，进一步支持药物再利用的概念。
这些药物可能为获得治疗反应提供额外机会。这种个体化肿瘤治疗方法不仅理论上适用于小细胞阴道癌，也适用于其他肿瘤实体。
