RNA-Based Therapeutics: Current Developments in Targeted Molecular Therapy of Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive cancer that has the highest mortality rate out of all breast cancer subtypes. Conventional clinical treatments targeting ER, PR, and HER2 receptors have been unsuccessful in the treatment of TNBC, which has led to various research efforts in developing new strategies to treat TNBC. Targeted molecular therapy of TNBC utilizes knowledge of key molecular signatures of TNBC that can be effectively modulated to produce a positive therapeutic response. Correspondingly, RNA-based therapeutics represent a novel tool in oncology with their ability to alter intrinsic cancer pathways that contribute to poor patient prognosis. Current RNA-based therapeutics exist as two major areas of investigation—RNA interference (RNAi) and RNA nanotherapy, where RNAi utilizes principles of gene silencing, and RNA nanotherapy utilizes RNA-derived nanoparticles to deliver chemotherapeutics to target cells. RNAi can be further classified as therapeutics utilizing either small interfering RNA (siRNA) or microRNA (miRNA). As the broader field of gene therapy has advanced significantly in recent years, so too have efforts in the development of effective RNA-based therapeutic strategies for treating aggressive cancers, including TNBC. This review will summarize key advances in targeted molecular therapy of TNBC, describing current trends in treatment using RNAi, combination therapies, and recent efforts in RNA immunotherapy, utilizing messenger RNA (mRNA) in the development of cancer vaccines.

TRIM65 Promotes Malignant Cell Behaviors in Triple-Negative Breast Cancer by Impairing the Stability of LATS1 Protein

“…Patients with breast cancer comprised 2.3 million new cases of cancer in 2020, accounting for approximately 11.7% of all tumors [ 1 ]. TNBC is the most aggressive type of breast cancer and is difficult to cure [ 24 ]. Hence, it is imperative to explore the molecular mechanism of TNBC and seek molecular targeted therapy for early TNBC.…”

Advancements in the Treatment of Triple-Negative Breast Cancer: A Narrative Review of the Literature

“…Tumor-specific neoantigens are derived from tumor somatic mutations and chromosomal rearrangements [ 64 , 65 ]. These neoantigens have been studied in RNA immunotherapy and their use in mRNA vaccines is a new and bright focus in the development of personalized cancer treatment [ 66 ]. The phase-I TNBC-MERIT trial (NCT02316457) [ 67 ] is currently studying RNA immunotherapy by utilizing two methods: the WAREHOUSE approach and the IVAC MUTANOME concept.…”

Advances in MUC1-Mediated Breast Cancer Immunotherapy

“…In the host, the transcription and translation of the DNA plasmid are performed, so an encoded antigen, usually the protein tumor marker that is processed into peptides, can be generated, and finally presented onto the surface of antigen-presenting cells (APCs) in hosts with MHC molecules. Afterward, neoantigen-specific T-cells can show the specific recognition of the peptide–MHC complex, thereby inducing cellular immunity in the host to resist specific antigen-bearing cancer cells [ 156 ]. Furthermore, these vaccines are lowly immunogenic, can be repeatedly injected, and induce extended antigenicity with immunity amplification, relative to additional vaccine types [ 157 , 158 ].…”

“…Finally, mRNA vaccines can be rapidly and massively produced, and the desired products are highly yielded under in vitro conditions, which is their most attractive advantage. mRNA vaccines have also been simplified, thus substantially reducing complications related to biological vaccine generation, such as environmental risk, genetic variability, and infectious agent processing [ 156 ].…”