Malla RamaRao, Bhamidipati Priyamvada, Samudrala Anuveda Sree, Nuthalapati Yerusha, Padmaraju Vasudevaraju, Malhotra Aditya, Rolig Annah S, Malhotra Sanjay V
Cancer Biology Group, Cancer Biology Laboratory, Department of Life Sciences, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, India.
Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA.
Cancers (Basel). 2025 Mar 30;17(7):1167. doi: 10.3390/cancers17071167.
Globally, breast cancer (BC) is the leading cause of cancer-related death for women. BC is characterized by heterogeneity, aggressive behavior, and high metastatic potential. Chemotherapy, administered as monotherapy or adjuvant therapy, remains a cornerstone of treatment; however, acquired drug resistance is a significant clinical challenge. Deciphering mechanisms of drug resistance will be central to developing more efficient treatment options and improving patient outcomes. The current review examines the multifaceted nature of exosomes in conferring drug resistance in BC through complex communication networks within the tumor microenvironment. We further explore recent advances in understanding how exosomes contribute to resistance against established chemotherapeutic agents such as tamoxifen, paclitaxel, doxorubicin, platinum-based drugs, trastuzumab, and newer immunotherapies, such as immune checkpoint inhibitors. Moreover, we discuss existing systematic approaches to investigating the exosome-drug resistance relationship in BC. Finally, we explore promising therapeutic approaches to overcome exosome-dependent drug resistance in BC, highlighting potential avenues for improved treatment efficacy. Investigating the distinct functions and cargo of exosomes offers potential for developing innovative approaches to overcoming treatment resistance.
在全球范围内，乳腺癌（BC）是女性癌症相关死亡的主要原因。BC具有异质性、侵袭性和高转移潜能等特征。作为单一疗法或辅助疗法使用的化疗仍然是治疗的基石；然而，获得性耐药是一个重大的临床挑战。破解耐药机制对于开发更有效的治疗方案和改善患者预后至关重要。本综述探讨了外泌体在通过肿瘤微环境中的复杂通讯网络赋予BC耐药性方面的多面性。我们进一步探讨了在理解外泌体如何导致对他莫昔芬、紫杉醇、阿霉素、铂类药物、曲妥珠单抗等既定化疗药物以及免疫检查点抑制剂等新型免疫疗法产生耐药性方面的最新进展。此外，我们讨论了现有的研究BC中外泌体与耐药性之间关系的系统方法。最后，我们探索了克服BC中外泌体依赖性耐药的有前景的治疗方法，强调了提高治疗效果的潜在途径。研究外泌体的独特功能和货物为开发克服治疗耐药性的创新方法提供了潜力。
