Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran.
Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran.
Drug Resist Updat. 2024 Sep;76:101119. doi: 10.1016/j.drup.2024.101119. Epub 2024 Jul 14.
Cancer metastasis and therapy resistance are intricately linked with the dynamics of Epithelial-Mesenchymal Transition (EMT) and Circulating Tumor Cells (CTCs). EMT hybrid cells, characterized by a blend of epithelial and mesenchymal traits, have emerged as pivotal in metastasis and demonstrate remarkable plasticity, enabling transitions across cellular states crucial for intravasation, survival in circulation, and extravasation at distal sites. Concurrently, CTCs, which are detached from primary tumors and travel through the bloodstream, are crucial as potential biomarkers for cancer prognosis and therapeutic response. There is a significant interplay between EMT hybrid cells and CTCs, revealing a complex, bidirectional relationship that significantly influences metastatic progression and has a critical role in cancer drug resistance. This resistance is further influenced by the tumor microenvironment, with factors such as tumor-associated macrophages, cancer-associated fibroblasts, and hypoxic conditions driving EMT and contributing to therapeutic resistance. It is important to understand the molecular mechanisms of EMT, characteristics of EMT hybrid cells and CTCs, and their roles in both metastasis and drug resistance. This comprehensive understanding sheds light on the complexities of cancer metastasis and opens avenues for novel diagnostic approaches and targeted therapies and has significant advancements in combating cancer metastasis and overcoming drug resistance.
癌症转移和治疗耐药性与上皮-间充质转化 (EMT) 和循环肿瘤细胞 (CTC) 的动态密切相关。具有上皮和间充质特征混合的 EMT 杂交细胞在转移中起着关键作用，并表现出显著的可塑性，使细胞状态发生转变，这些转变对细胞内渗、循环中存活和远处部位外渗至关重要。同时，从原发性肿瘤脱落并通过血液传播的 CTC 是癌症预后和治疗反应的潜在生物标志物，具有重要意义。EMT 杂交细胞和 CTC 之间存在显著的相互作用，揭示了一种复杂的、双向关系，这种关系显著影响转移进展，并在癌症药物耐药性中起着关键作用。这种耐药性还受到肿瘤微环境的影响，肿瘤相关巨噬细胞、癌症相关成纤维细胞和缺氧等因素驱动 EMT 并导致治疗耐药性。了解 EMT 的分子机制、EMT 杂交细胞和 CTC 的特征以及它们在转移和耐药性中的作用非常重要。这种全面的理解揭示了癌症转移的复杂性，并为新的诊断方法和靶向治疗开辟了途径，并在对抗癌症转移和克服药物耐药性方面取得了显著进展。
