Berckmans Yani, Hoffert Yannick, Vankerckhoven Ann, Dreesen Erwin, Coosemans An
Laboratory of Tumor Immunology and Immunotherapy, Department of Oncology, Leuven Cancer Institute, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
Clinical Pharmacology and Pharmacotherapy Unit, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
Pharmaceutics. 2023 Jun 22;15(7):1792. doi: 10.3390/pharmaceutics15071792.
The lethality of patients with ovarian cancer (OC) remains high. Current treatment strategies often do not lead to the desired outcome due to the development of therapy resistance, resulting in high relapse rates. Additionally, clinical trials testing immunotherapy against OC have failed to reach significant results to date. The OC tumor microenvironment and specifically myeloid-derived suppressor cells (MDSC) are known to generate immunosuppression and inhibit the anti-tumor immune response following immunotherapy treatment. Our review aims to characterize potential candidate treatments to target MDSC in OC through drug-repurposing. A literature search identified repurposable compounds with evidence of their suppressing the effect of MDSC. A total of seventeen compounds were withheld, of which four were considered the most promising. Lurbinectedin, metformin, celecoxib, and 5-azacytidine have reported preclinical effects on MDSC and clinical evidence in OC. They have all been approved for a different indication, characterizing them as the most promising candidates for repurposing to treat patients with OC.
卵巢癌（OC）患者的致死率仍然很高。由于治疗耐药性的出现，当前的治疗策略往往无法达到预期效果，导致高复发率。此外，迄今为止，针对OC的免疫疗法临床试验尚未取得显著成果。已知OC肿瘤微环境，特别是髓系来源的抑制细胞（MDSC）会产生免疫抑制，并在免疫治疗后抑制抗肿瘤免疫反应。我们的综述旨在通过药物再利用来确定针对OC中MDSC的潜在候选治疗方法。文献检索确定了具有抑制MDSC作用证据的可再利用化合物。总共筛选出十七种化合物，其中四种被认为最有前景。鲁比卡丁、二甲双胍、塞来昔布和5-氮杂胞苷已报道对MDSC有临床前作用以及在OC中的临床证据。它们均已获批用于不同适应症，这使其成为最有前景的用于治疗OC患者的再利用候选药物。
