Abstract
Therapy resistance is a characteristic of cancer cells that significantly reduces the effectiveness of drugs. Despite the popularity of cisplatin (CP) as a chemotherapeutic agent, which is widely used in the treatment of various types of cancer, resistance of cancer cells to CP chemotherapy has been extensively observed. Among various reported mechanism(s), the epithelial–mesenchymal transition (EMT) process can significantly contribute to chemoresistance by converting the motionless epithelial cells into mobile mesenchymal cells and altering cell–cell adhesion as well as the cellular extracellular matrix, leading to invasion of tumor cells. By analyzing the impact of the different molecular pathways such as microRNAs, long non-coding RNAs, nuclear factor-κB (NF-ĸB), phosphoinositide 3-kinase-related protein kinase (PI3K)/Akt, mammalian target rapamycin (mTOR), and Wnt, which play an important role in resistance exhibited to CP therapy, we first give an introduction about the EMT mechanism and its role in drug resistance. We then focus specifically on the molecular pathways involved in drug resistance and the pharmacological strategies that can be used to mitigate this resistance. Overall, we highlight the various targeted signaling pathways that could be considered in future studies to pave the way for the inhibition of EMT-mediated resistance displayed by tumor cells in response to CP exposure.
Highlights
Cancer is still an increasing challenge for public health and is the second leading cause of death worldwide [1]
14, 15-EET trigger epithelial–mesenchymal transition (EMT) through activation of FAK/PI3K/Akt and αvβ3 integrin to ensure the resistance of cancer cells in CP chemotherapy
In the first section we have shown that the administration of CP is associated with EMT and tumor cell resistance
Summary
Cancer is still an increasing challenge for public health and is the second leading cause of death worldwide [1]. It is less likely to diagnose aged patients with cancer at early and local stages [3] These statements are in agreement with the fact that dealing with cancer is of the utmost importance in the modern world and it demands extensive research into finding novel treatments for this life threatening disorder [4,5,6,7,8,9,10,11]. Finding an effective regimen for inhibition of chemoresistance in cancer therapy relies on revealing the molecular pathways and mechanisms involved in development of resistance of cancer cells to chemotherapy. It has been possible to implicate the process of EMT in drug resistance and directing further studies towards targeting EMT in suppressing resistance developed against CP treatment
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