RAS: Circuitry and therapeutic targeting

Abstract

Cancer has affected the lives of millions worldwide and is truly regarded as a devastating disease process. Despite advanced understanding of the genomic underpinning of cancer development and progression, therapeutic challenges are still persistent. Among all the human cancers, around 33% are attributed to mutations in RAS oncogene, a crucial component of the signaling pathways. With time, our understanding of RAS circuitry has improved and now the fact that it activates several downstream effectors, depending on the type and grades of cancer has been established. The circuitry is controlled via post-transcriptional mechanisms and frequent distortions in these mechanisms lead to important metabolic as well as immunological states that favor cancer cells' growth, survival, plasticity and metastasis. Therefore, understanding RAS circuitry can help researchers/clinicians to develop novel and potent therapeutics that, in turn, can save the lives of patients suffering from RAS-mutant cancers. There are many challenges presented by resistance and the potential strategies with a particular focus on novel combinations for overcoming these, that could move beyond transitory responses in the direction of treatment. Here in this review, we will look at how understanding the circuitry of RAS can be put to use in making strategies for developing therapeutics against RAS- driven malignancies.