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Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer.

ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs that can post-transcriptionally regulate the genes involved in critical cellular processes. The aberrant expressions of oncogenic or tumor suppressor miRNAs have been associated with cancer progression and malignancies. This resulted in the dysregulation of signaling pathways involved in cell proliferation, apoptosis and survival, metastasis, cancer recurrence and chemoresistance. In this review, we will first (i) provide an overview of the miRNA biogenesis pathways, and in vitro and in vivo models for research, (ii) summarize the most recent findings on the roles of microRNAs (miRNAs) that could potentially be used for miRNA-based therapy in the treatment of breast cancer and (iii) discuss the various therapeutic applications.

SUBMITTER: Wong JS

PROVIDER: S-EPMC7549352 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer.

Wong Jun Sheng JS Cheah Yoke Kqueen YK

Non-coding RNA 20200713 3

MicroRNAs (miRNAs) are small non-coding RNAs that can post-transcriptionally regulate the genes involved in critical cellular processes. The aberrant expressions of oncogenic or tumor suppressor miRNAs have been associated with cancer progression and malignancies. This resulted in the dysregulation of signaling pathways involved in cell proliferation, apoptosis and survival, metastasis, cancer recurrence and chemoresistance. In this review, we will first (i) provide an overview of the miRNA biog ...[more]

PMID: 32668603

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Project description:Progress in the treatment of cancer over the past decade has been slow. Targeting a mutated gene of an individual patient tumor, tumor-guided agents, and the first draft of the human genome sequence have created an overenthusiasm to achieve personalized medicine. However, we now know that this effort is misleading. Extreme interpatient and intratumor heterogeneity, scarce knowledge in how genome-wide mutational landscape and epigenetic changes affect transcriptional processes, gene expression, signaling transduction networks and cell regulation, and clinical assessment of temporary efficacy of targeted drugs explain the limitations of these currently available agents. Trastuzumab and a few other monoclonal antibodies or small-molecule tyrosine kinase inhibitors (TKIs) represent an exception to this rule. By blocking ligand-binding receptor in patients with human epidermal growth factor receptor 2 (HER2) amplification and overexpression, trastuzumab added to chemotherapy in HER2-positive patients has been proven to provide significant overall survival benefit in both metastatic and adjuvant settings. Lapatinib, a small-molecule dual inhibitor (TKI) of both HER2 and EGFR (epidermal growth factor receptor) pathways, has an antitumor activity translated into progression-free survival benefit in HER2-positive metastatic patients previously treated with a taxane, an anthracycline, and trastuzumab. Despite these advances, ~25% of patients with HER2-positive breast cancer experience recurrence in the adjuvant setting, while in the metastatic setting, median survival time is 25 months. In this review, we discuss the safety, efficacy, and limitations of the trastuzumab emtansine (T-DM1) conjugate in the treatment of HER2-positive metastatic breast cancer. We also highlight Phase III randomized trials, currently underway, using either the T-DM1 conjugate or various combinations of monoclonal antibodies and TKIs. Moreover, in contrast with all these agents developed on the basis of "central dogma" of simplified reductionist transcription and single gene-phenotype linear relationship, we summarize the emerging, amazing era of next-generation, transcriptional circuitry and intracellular signaling network-based drugs guided by the latest advances in genome science and dynamics of network biology.

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Dataset Information

Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer.

Publications

Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer.

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