Cell Metabolism：中山大学潘超云团队等揭示抗抑郁药物增强卵巢癌化疗敏感性的机制

Core Viewpoint - The study reveals that peripheral serotonin enhances DNA homologous recombination repair in ovarian cancer cells through tumor-associated macrophages (TAM), leading to chemotherapy resistance. It proposes the use of the selective serotonin reuptake inhibitor (SSRI) fluoxetine as a potential sensitizer for chemotherapy [1][5]. Group 1: Mechanism of Action - A specific subset of serotonin-sensitive TAM enhances homologous recombination repair in ovarian tumors, which are less responsive to chemotherapy [2][3]. - Peripheral serotonin activates TAM via the HTR7 receptor, triggering the secretion of inositol metabolic enzymes PI4K2A and ITPKC [2]. - These enzymes are delivered to cancer cells through extracellular vesicles (EV), increasing intracellular levels of inositol-1,3,4,5-tetrakisphosphate (IP4), which binds to MRE11 protein and promotes its interaction with DNA, thereby enhancing homologous recombination repair [2][6]. Group 2: Implications for Treatment - The study introduces a cross-system regulatory axis involving neurotransmitters, immune cells, metabolic interactions, and tumor DNA damage repair [5]. - It highlights the potential application of SSRIs like fluoxetine as chemotherapy sensitizers, indicating a new targeted approach to modulate homologous recombination repair beyond cancer cell autonomous regulation [5][6].