更深入地了解转移性癌症的进展； 上皮间质转化和基因组不稳定性：对治疗耐药性的影响

Title:Deeper Insight in Metastatic Cancer Progression; Epithelial-to- Mesenchymal Transition and Genomic Instability: Implications on Treatment Resistance

Volume: 21 Issue: 10

关键词: 癌症、EMT、治疗抗性、干性、DNA 损伤修复、分子相互作用。

摘要: Therapy resistance remains the major obstacle to successful cancer treatment. Epithelial-to- mesenchymal transition [EMT], a cellular reprogramming process involved in embryogenesis and organ development and regulated by a number of transcriptional factors [EMT-TFs] such as ZEB1/2, is recognized for its role in tumor progression and metastasis. Recently, a growing body of evidence has implicated EMT in cancer therapy resistance, but the actual mechanism that underlies this finding has remained elusive. For example, whether it is, the EMT states in itself or the EMT-TFs that modulate chemo or radio-resistance in cancer is still contentious. Here, we summarise the molecular mechanisms of the EMT program and chemotherapeutic resistance in cancer with specific reference to DNA damage response [DDR]. We provide an insight into the molecular interactions that exist between EMT program and DNA repair machinery in cancer and how this interaction influences therapeutic response. We review conflicting studies linking EMT and drug resistance via the DNA damage repair axis. We draw scientific evidence demonstrating how several molecular signalling, including EMT-TFs, work in operational harmony to induce EMT and confer stemness properties on the EMT-susceptible cells. We highlight the role of enhanced DNA damage repair system associated with EMT-derived stem cell-like states in promoting therapy resistance and suggest a multi-targeting modality in combating cancer treatment resistance.

Cite this article as:

Deeper Insight in Metastatic Cancer Progression; Epithelial-to- Mesenchymal Transition and Genomic Instability: Implications on Treatment Resistance, Current Molecular Medicine 2021; 21 (10) . https://dx.doi.org/10.2174/1566524021666210202114844