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Cancer is a class of disease that involves an uncontrolled cell growth with a potential to vigorously invade into the adjacent issue or metastasize to the distant sites of the body. With regard to the severe health problems triggered by cancer, numerous investigations applying RNA therapeutics for cancer treatment have been carried out. In terms of cancer targeting, therapeutic modalities have been developed involving either short non-coding RNAs (siRNA or miRNA) or in vitro transcribed (IVT) mRNA. Despite the biological barriers induced from the abnormal status of the cancer tissue, cancer-target delivery system with a deep tissue penetrating ability has been developed to overcome such issues.
The use of RNAi for cancer treatment focuses on the diverse signaling pathways related to tumor growth and metastasis. For example, one of the most widely used methods is to incorporate siRNAs against genes related to angiogenesis pathway (such as vascular endothelial growth factor: VEGF). Another major strategy focuses on the interruption of carcinogenesis by inhibition of the associated pathways involving the protein tyrosine kinase (PTK), EGFR, HER2, PI3K, NF-κB, and HIF-1.
Compelling evidences have demonstrated that miRNAs function as either oncogenes or tumor suppressors. An increasing number of studies have identified miRNAs as potential biomarkers for human cancer diagnosis, prognosis and therapeutic targets or tools. For example, the miR-34 family, including miR-34a, miR-34b and miR-34c, are cancer-suppressive miRNAs, inducing growth arrest, APOP, and metastasis inhibition.
Tumor-associated or specific antigen-encoding mRNA could be delivered and expressed in APCs such as DC, resulting in the stimulation and proliferation of cytotoxic T lymphocyte (CTL) specific for the administered antigen. As shown (Fig 1), When mRNA cancer vaccines are injected intradermally, they induce the activation of skin-resident immature DCs. Activated DCs migrate to the secondary lymphoid organ, thereby transducing proliferation and the activation signal to naive CD8+ T cells. Fully activated effector CD8+ T cells show an antitumor effect against the specific cancer cells which express the antigen encoded by injected IVT mRNA.
Fig1. Mechanism of mRNA cancer vaccines.
Despite the challenging obstacles, RNA-target therapeutics have a significant impact on the diagnosis and treatment of cancer. In addition, the combination of genetic diagnosis using next-generation sequencing and RNA-target therapy may provide effective precision medicine for cancer patients.