Cargando…

MicroRNAs as Potential Predictors of Response to CDK4/6 Inhibitor Treatment

SIMPLE SUMMARY: MicroRNAs are endogenous non-coding 20–22 nucleotide long RNAs that play a fundamental role in the post-transcriptional control of gene expression. Consequently, microRNAs are involved in multiple biological processes of cancer and could be used as biomarkers with prognostic and pred...

Descripción completa

Detalles Bibliográficos
Autores principales: Andrikopoulou, Angeliki, Shalit, Almog, Zografos, Eleni, Koutsoukos, Konstantinos, Korakiti, Anna-Maria, Liontos, Michalis, Dimopoulos, Meletios-Athanasios, Zagouri, Flora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391635/
https://www.ncbi.nlm.nih.gov/pubmed/34439268
http://dx.doi.org/10.3390/cancers13164114
Descripción
Sumario:SIMPLE SUMMARY: MicroRNAs are endogenous non-coding 20–22 nucleotide long RNAs that play a fundamental role in the post-transcriptional control of gene expression. Consequently, microRNAs are involved in multiple biological processes of cancer and could be used as biomarkers with prognostic and predictive significance. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have become a mainstay of treatment for patients with advanced hormone receptor-positive (HR) breast cancer. Despite the initial high response rates, approximately 10% of patients demonstrate primary resistance to CDK4/6 inhibitors while acquired resistance is almost inevitable. Considering the fundamental role of miRNAs in tumorigenesis, we aimed to explore the potential involvement of microRNAs in response to CDK4/6 inhibition in solid tumors. A number of microRNAs were shown to confer resistance or sensitivity to CDK4/6 inhibitors in preclinical studies, although this remains to be proved in human studies. ABSTRACT: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as novel treatment options in the management of advanced or metastatic breast cancer. MicroRNAs are endogenous non-coding 19–22-nucleotide-long RNAs that regulate gene expression in development and tumorigenesis. Herein, we systematically review all microRNAs associated with response to CDK4/6 inhibitors in solid tumors and hematological malignancies. Eligible articles were identified by a search of the MEDLINE and ClinicalTrials.gov databases for the period up to1 January 2021; the algorithm consisted of a predefined combination of the words “microRNAs”, “cancer” and “CDK 4/6 inhibitors”. Overall, 15 studies were retrieved. Six microRNAs (miR-126, miR-326, miR3613-3p, miR-29b-3p, miR-497 and miR-17-92) were associated with sensitivity to CDK4/6 inhibitors. Conversely, six microRNAs (miR-193b, miR-432-5p, miR-200a, miR-223, Let-7a and miR-21) conferred resistance to treatment with CDK4/6 inhibitors. An additional number of microRNAs (miR-124a, miR9, miR200b and miR-106b) were shown to mediate cellular response to CDK4/6 inhibitors without affecting sensitivity to treatment. Collectively, our review provides evidence that microRNAs could serve as predictive biomarkers for treatment with CDK4/6 inhibitors. Moreover, microRNA-targeted therapy could potentially maximize sensitivity to CDK4/6 inhibition.