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MiR 221/222 as New Players in Tamoxifen Resistance
Nafiseh Sadat Alamolhodaei, Javad Behravan, Fatemeh Mosaffa
1Pharmaceutical Research Center, Pharmacy School, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
Breast cancer is the most frequent cancer in women. Despite advances in early detection and treatment, it has the second highest mortality rate after lung cancer. Around 85% of breast carcinomas are ER+; thus, antiestrogens like tamoxifen are beneficial. Although, tamoxifen is useful for many patients, a number of patients respond poorly to initial therapy or recurrence occurs in about 30% of cases, because tamoxifen resistance happens. Drug resistance remains a major clinical obstacle to successful treatment of breast cancer and more than 90% of unsuccessful treatments are because of acquired resistance and MultiDrug Resistance (MDR) is a major contributor. MicroRNAs are members of a novel class of short noncoding RNAs. Besides their various roles in gene expression, miRNAs are considered as important cancer therapeutic targets and biomarkers. Since 2005, when miRNA deregulation was first reported in breast cancer, more than 1000 reports have been published about miRNAs. Increasing number of studies showed the importance of miRNAs in antiestrogen therapy, especially on tamoxifen; thus, it is not surprising that these tiny molecules are involved in drug resistance. Due to the pivotal role of these known RNA molecules, in this review, we tried to illustrate the importance of the miRNAs as a new player in breast cancer pathogenesis. We have also focused on cancer drug resistance mechanisms highlighting the role of important oncomirs, miR 221/222, involved in cell cycle deregulation in breast cancer. The relationship between these oncomiRs with resistance to tamoxifen is also emphasized.
Insights
MicroRNAs play a crucial role in breast cancer development and tamoxifen resistance. Understanding these microRNAs (miRNAs) offers new therapeutic targets for overcoming drug resistance in estrogen receptor-positive breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer is the most frequent cancer in women, with estrogen receptor-positive (ER+) subtypes benefiting from antiestrogen therapies like tamoxifen.
- Tamoxifen resistance and multi-drug resistance (MDR) significantly impede treatment success, contributing to over 90% of treatment failures.
- MicroRNAs (miRNAs) are short noncoding RNAs involved in gene expression and are increasingly recognized as key players in cancer pathogenesis and therapeutic resistance.
Purpose of the Study:
- To review the significance of miRNAs in breast cancer pathogenesis.
- To highlight the role of miRNAs in the development of tamoxifen resistance.
- To focus on specific oncomiRs, miR 221/222, and their involvement in cell cycle deregulation and tamoxifen resistance.
Main Methods:
- Literature review of studies on miRNAs in breast cancer.
- Analysis of the role of miRNAs in antiestrogen therapy and drug resistance mechanisms.
- Focus on oncomiRs miR 221/222 and their association with tamoxifen resistance.
Main Results:
- miRNA deregulation is a significant factor in breast cancer.
- miRNAs are implicated in the development of tamoxifen resistance.
- OncomiRs, specifically miR 221/222, are involved in cell cycle deregulation and contribute to tamoxifen resistance in breast cancer.
Conclusions:
- miRNAs represent a novel and important factor in breast cancer pathogenesis.
- Targeting miRNAs may offer new strategies to overcome tamoxifen resistance.
- Further research into miRNAs, like miR 221/222, is crucial for developing effective breast cancer treatments.
