Gene Silencing Agents in Breast Cancer

Abstract

MicroRNAs (miRs) are a class of non-coding RNAs, approximately 20-25 nucleotides long, discovered in the nematode, Caenorhabditis elegans, in 1993. There are two primary categories of non-coding RNA (ncRNA): (1) short interfering RNAs (siRNA) and (2) microRNAs (miRs). In general, miRs control protein production via partially complementary binding of the mRNA 3′UTRs. Both siRNAs and miRNAs are critical regulators of developmental and homeostatic processes as well as disease pathogenesis. While the treatment of advanced stage breast cancer presents several challenges, the development of therapeutic resistance contributes to a high mortality rate. Dysregulation of miR expression has been implicated in progression of breast cancer disease. Moreover, miRs have been found to play a role in the development of drug resistance. In this context, one of the therapeutic potentials of miRNAs is the correlation of circulating miR levels with breast cancer progression stages and disease phenotypes. Secondly, researchers are investigating novel delivery strategies for the substitution or silencing of ncRNAs involved in the disease. This chapter describes both the general miRNA mechanism of actions and the miRNAs related to breast cancer research. It is specifically designed for breast cancer researchers with expertise in gene delivery, clinicians, and clinical translational scientists.

Bioengineered siRNA-Based Nanoplatforms Targeting Molecular Signaling Pathways for the Treatment of Triple Negative Breast Cancer: Preclinical and Clinical Advancements

“…From the molecular level and according to the expression and/or lack expression of hormone receptors (HR); estrogen receptors (ER) and progesterone receptors (PR) and HER-2 on breast cancerous cells, breast cancer is categorized into four subtypes: Luminal A and B characterized by expression of hormonal receptors with or without HER-2, basal-like cancerous cells where the three hormonal receptors are deficient, so they are commonly known as triple negative breast cancer (TNBC), and HER-2 enriched cancer that is enriched with HER-2 only [ 6 , 8 ]. Among the different subtypes of breast cancer, TNBC is clinically deliberated to be the most aggressive form with poorer prognosis that attributes for patients’ death within five years post-diagnosis [ 9 ].…”

“…To date, there are no FDA-approved targeted therapies for treating this aggressive form of breast cancer [ 11 ]. Patients with TNBC are treated systemically with chemotherapeutic agents which include anthracyclines and taxanes [ 8 , 12 ]. Numerous obstacles compromise the clinical usefulness of these medications, and some of these obstacles are related to the disease itself; as cancerous cells should not only be treated for their uncontrolled cell proliferation, rather integration of cancer metastasis activity, the heterogeneity of the tumor microenvironment, and the complexity of the signaling pathways must be contemplated in choosing appropriate treatment [ 13 ].…”