Bonechi Francesca, Bacci Marina, Lorito Nicla, Smiriglia Alfredo, Pagliantini Edoardo, Benelli Matteo, Meattini Icro, Morandi Andrea
Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy.
Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3, 50134, Florence, Italy.
Mol Cell Biochem. 2025 May 23. doi: 10.1007/s11010-025-05308-w.
Endocrine therapy (ET) is essential for managing ER+ HER2- breast cancer; however, resistance remains a significant clinical challenge. This study investigated whether CD44-SLC1A2 gene fusions, reported in gastrointestinal malignancies, contribute to ET resistance mechanisms in breast cancer. Although no CD44-SLC1A2 fusions were detected, high expression of CD44 and SLC1A2 was associated with poor survival outcomes and identified a therapy-resistant subpopulation sustained by aspartate and glutamate metabolism, highlighting potential metabolic vulnerabilities for future therapeutic intervention.
内分泌治疗（ET）对于治疗雌激素受体阳性（ER+）、人表皮生长因子受体2阴性（HER2-）乳腺癌至关重要；然而，耐药性仍然是一个重大的临床挑战。本研究调查了在胃肠道恶性肿瘤中报道的CD44-SLC1A2基因融合是否与乳腺癌的内分泌治疗耐药机制有关。虽然未检测到CD44-SLC1A2融合，但CD44和SLC1A2的高表达与不良生存结果相关，并确定了一个由天冬氨酸和谷氨酸代谢维持的治疗抵抗亚群，突出了未来治疗干预的潜在代谢弱点。
