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探索抗体药物偶联物在卵巢癌治疗中的治疗用途及疗效。

Exploring the therapeutic use and outcome of antibody-drug conjugates in ovarian cancer treatment.

作者信息

Narayana Revu V L, Gupta Romi

机构信息

Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.

O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL, USA.

出版信息

Oncogene. 2025 May 27. doi: 10.1038/s41388-025-03448-3.

Abstract

Ovarian cancer remains a leading cause of cancer-related deaths due to late-stage diagnosis and treatment resistance. While surgery and chemotherapy are standard treatments, challenges such as platinum resistance, tumor heterogeneity, and limited therapeutic options persist. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic strategy for treating ovarian cancer (OC), particularly in cases of platinum-resistant ovarian cancer (PROC). In OC, various ADCs targeting antigens such as folate receptor alpha (FRα), trophoblast cell surface antigen 2 (TROP-2), mesothelin (MSLN), sodium-dependent phosphate transport protein 2B (NaPi2b), and human epidermal growth factor receptor 2 (HER2) have shown encouraging preclinical results and significant clinical activity. However, challenges like antigen heterogeneity, off-target toxicity, and resistance mechanisms remain. This review highlights the current ADCs used in the clinic for the treatment of ovarian cancer, their challenges, and the future potential of ADC-based therapies in overcoming resistance and improving patient outcomes.

摘要

由于晚期诊断和治疗耐药性,卵巢癌仍然是癌症相关死亡的主要原因。虽然手术和化疗是标准治疗方法,但铂耐药、肿瘤异质性和治疗选择有限等挑战依然存在。抗体药物偶联物(ADC)已成为治疗卵巢癌(OC)的一种有前景的治疗策略,特别是在铂耐药卵巢癌(PROC)的情况下。在OC中,各种靶向抗原如叶酸受体α(FRα)、滋养层细胞表面抗原2(TROP-2)、间皮素(MSLN)、钠依赖性磷酸盐转运蛋白2B(NaPi2b)和人表皮生长因子受体2(HER2)的ADC已显示出令人鼓舞的临床前结果和显著的临床活性。然而,抗原异质性、脱靶毒性和耐药机制等挑战仍然存在。本综述重点介绍了目前临床上用于治疗卵巢癌的ADC、它们面临的挑战以及基于ADC的疗法在克服耐药性和改善患者预后方面的未来潜力。

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