Targeting miRNAs involved in cancer stem cell and EMT regulation: An emerging concept in overcoming drug resistance.
Although chemotherapy is an important therapeutic strategy for cancer treatment, it fails to eliminate all tumor cells due to intrinsic or acquired drug resistance, which is the most common cause of tumor recurrence. Emerging evidence suggests an intricate role of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT)-type cells in anticancer drug resistance. Recent studies also demonstrated that microRNAs (miRNAs) play critical roles in the regulation of drug resistance. Here we will discuss current knowledge regarding CSCs, EMT and the role of regulation by miRNAs in the context of drug resistance, tumor recurrence and metastasis. A better understanding of the molecular intricacies of drug-resistant cells will help to design novel therapeutic strategies by selective targeting of CSCs and EMT-phenotypic cells through alterations in the expression of specific miRNAs towards eradicating tumor recurrence and metastasis. A particular promising lead is the potential synergistic combination of natural compounds that affect critical miRNAs, such as curcumin or epigallocatechin-3-gallate (EGCG) with chemotherapeutic agents.
Wang
Zhiwei
Z
Department of Pathology, Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI 48201, USA. zhiweiwang@med.wayne.edu
Li
Yiwei
Y
Ahmad
Aamir
A
Azmi
Asfar S
AS
Kong
Dejuan
D
Banerjee
Sanjeev
S
Sarkar
Fazlul H
FH
D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D028321:Plant Preparations / Q000378:metabolism / Q000494:pharmacology
D000970:Antineoplastic Agents; D035683:MicroRNAs; D028321:Plant Preparations