乳腺癌是一种在乳腺早期就表现出恶性肿瘤的分类。在乳腺癌亚型中，三阴性乳腺癌（TNBC）表现出最具侵略性的行为，具有显著的干细胞特征。由于对激素治疗和特定靶向治疗方法缺乏反应，化疗仍然是TNBC治疗的第一线。然而，对化疗药物的耐药性的获取增加了治疗失败的可能性，并促进了癌症复发和远处转移。侵袭性原发性肿瘤是癌症负担的发源地，而转移是TNBC相关的发病率和死亡率的关键属性。通过具有亲和力的特异性治疗剂靶向化疗耐药性转移起始细胞是TNBC临床管理的有前途的一步。探索肽作为具有特异性作用、低免疫原性和强大疗效的生物相容实体的能力，为设计基于肽的药物提供了原则，从而增加目前化疗药物的疗效，选择性地靶向耐药的TNBC细胞。在这里，我们首先关注TNBC细胞获得耐药性以逃避化疗药物影响的机制。接下来，描述利用肿瘤靶向肽的新型治疗方法来利用TNBC的化疗抵抗机制的原理。版权所有© 2023年Elsevier Inc.。保留所有权利。

Breast cancer is a collation of malignancies that manifest in the mammary glands at the early stages. Among breast cancer subtypes, triple-negative breast cancer (TNBC) shows the most aggressive behavior, with apparent stemness features. Owing to the lack of response to hormone therapy and specific targeted therapies, chemotherapy remains the first line of the TNBC treatment. However, the acquisition of resistance to chemotherapeutic agents increase therapy failure, and promotes cancer recurrence and distant metastasis. Invasive primary tumors are the birthplace of cancer burden, though metastasis is a key attribute of TNBC-associated morbidity and mortality. Targeting the chemoresistant metastases-initiating cells via specific therapeutic agents with affinity to the upregulated molecular targets is a promising step in the TNBC clinical management. Exploring the capacity of peptides as biocompatible entities with the specificity of action, low immunogenicity, and robust efficacy provides a principle for designing peptide-based drugs capable of increasing the efficacy of current chemotherapy agents for selective targeting of the drug-tolerant TNBC cells. Here, we first focus on the resistance mechanisms that TNBC cells acquire to evade the effect of chemotherapeutic agents. Next, the novel therapeutic approaches employing tumor-targeting peptides to exploit the mechanisms of drug resistance in chemorefractory TNBC are described.Copyright © 2023 Elsevier Inc. All rights reserved.