Wallace-Povirk Adrianne, Hou Zhanjun, Nayeen Md Junayed, Gangjee Aleem, Matherly Larry H
Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, 421 East Canfield Street, Detroit, MI 48201, USA.
Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Cancers (Basel). 2021 Dec 31;14(1):191. doi: 10.3390/cancers14010191.
New therapies are urgently needed for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. To identify new approaches for targeting EOC, metabolic vulnerabilities must be discovered and strategies for the selective delivery of therapeutic agents must be established. Folate receptor (FR) α and the proton-coupled folate transporter (PCFT) are expressed in the majority of EOCs. FRβ is expressed on tumor-associated macrophages, a major infiltrating immune population in EOC. One-carbon (C1) metabolism is partitioned between the cytosol and mitochondria and is important for the synthesis of nucleotides, amino acids, glutathione, and other critical metabolites. Novel inhibitors are being developed with the potential for therapeutic targeting of tumors via FRs and the PCFT, as well as for inhibiting C1 metabolism. In this review, we summarize these exciting new developments in targeted therapies for both tumors and the tumor microenvironment in EOC.
上皮性卵巢癌（EOC）是最致命的妇科恶性肿瘤，迫切需要新的治疗方法。为了确定针对EOC的新方法，必须发现代谢脆弱性，并建立治疗药物的选择性递送策略。叶酸受体（FR）α和质子偶联叶酸转运体（PCFT）在大多数EOC中表达。FRβ在肿瘤相关巨噬细胞上表达，肿瘤相关巨噬细胞是EOC中主要的浸润免疫细胞群。一碳（C1）代谢在细胞质和线粒体之间进行分配，对核苷酸、氨基酸、谷胱甘肽和其他关键代谢物的合成很重要。正在开发新型抑制剂，其有可能通过FRs和PCFT对肿瘤进行治疗靶向，以及抑制C1代谢。在这篇综述中，我们总结了EOC中针对肿瘤和肿瘤微环境的靶向治疗的这些令人兴奋的新进展。
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