Over the past two decades, significant technological innovations have led to messenger RNA (mRNA) becoming a promising option for developing prophylactic and therapeutic vaccines, protein replacement therapies, and genome engineering. The success of the two COVID-19 mRNA vaccines has sparked new enthusiasm for other medical applications, particularly in cancer treatment. In vitro-transcribed (IVT) mRNAs are structurally designed to resemble naturally occurring mature mRNA. Delivery of IVT mRNA via delivery platforms such as lipid nanoparticles allows host cells to produce many copies of encoded proteins, which can serve as antigens to stimulate immune responses or as additional beneficial proteins for supplements. mRNA-based cancer therapeutics include mRNA cancer vaccines, mRNA encoding cytokines, chimeric antigen receptors, tumor suppressors, and other combination therapies. To better understand the current development and research status of mRNA therapies for cancer treatment, this review focused on the molecular design, delivery systems, and clinical indications of mRNA therapies in cancer.
The Rat Sarcoma (RAS) family (NRAS, HRAS, and KRAS) is endowed with GTPase activity to regulate various signaling pathways in ubiquitous animal cells. As proto-oncogenes, RAS mutations can maintain activation, leading to the growth and proliferation of abnormal cells and the development of a variety of human cancers. For the fight against tumors, the discovery of RAS-targeted drugs is of high significance. On the one hand, the structural properties of the RAS protein make it difficult to find inhibitors specifically targeted to it. On the other hand, targeting other molecules in the RAS signaling pathway often leads to severe tissue toxicities due to the lack of disease specificity. However, computer-aided drug design (CADD) can help solve the above problems. As an interdisciplinary approach that combines computational biology with medicinal chemistry, CADD has brought a variety of advances and numerous benefits to drug design, such as the rapid identification of new targets and discovery of new drugs. Based on an overview of RAS features and the history of inhibitor discovery, this review provides insight into the application of mainstream CADD methods to RAS drug design.
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