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Understanding and drugging RAS: 40 years to break the tip of the iceberg
Donita C Brady1,2, Julija Hmeljak3, Arvin C Dar4
1Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abstract:
Several cancers and rare genetic diseases are caused by dysregulation in the RAS signaling pathway. RAS proteins serve as molecular switches that regulate pathways involved in cellular growth, differentiation and survival. These pathways have been an intense area of investigation for four decades, since the initial identification of somatic RAS mutations linked to human cancers. In the past few years, inhibitors against several RAS effectors, as well as direct inhibitors of the K-RAS mutant G12C, have been developed. This Special Issue in DMM includes original Research articles on RAS-driven cancers and RASopathies. The articles provide insights into mechanisms and biomarkers, and evaluate therapeutic targets. Several articles also present new disease models, whereas others describe technologies or approaches to evaluate the function of RAS in vivo. The collection also includes a series of Review articles on RAS biology and translational aspects of defining and treating RAS-driven diseases. In this Editorial, we summarize this collection and discuss the potential impact of the articles within this evolving area of research. We also identify areas of growth and possible future developments.
Insights
Dysregulation of the RAS signaling pathway causes cancers and genetic diseases. New research explores RAS-driven diseases, focusing on mechanisms, biomarkers, and therapeutic targets for better treatments.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- The RAS signaling pathway is crucial for cellular functions, and its dysregulation is linked to various cancers and rare genetic disorders.
- Decades of research have focused on RAS proteins due to their role as molecular switches in cell growth and survival.
- Somatic RAS mutations identified in human cancers have driven extensive investigation into this pathway.
Discussion:
- This Special Issue compiles research on RAS-driven cancers and RASopathies, offering insights into underlying mechanisms and potential biomarkers.
- Therapeutic targets for RAS-driven diseases are being evaluated, with recent advancements in developing inhibitors for RAS effectors and specific K-RAS mutants.
- The collection includes novel disease models and innovative technologies for assessing RAS protein function in vivo.
Key Insights:
- Recent developments include inhibitors targeting RAS effectors and the K-RAS G12C mutant.
- The Special Issue presents a comprehensive overview of RAS biology and the translational aspects of treating RAS-driven diseases.
- New disease models and in vivo functional evaluation technologies are highlighted.
Outlook:
- Future research will likely focus on refining therapeutic strategies and biomarkers for RAS-driven malignancies and genetic conditions.
- Continued exploration of RAS biology is expected to yield further insights into disease mechanisms and treatment possibilities.
- The field is poised for growth, with potential for significant advancements in defining and treating RAS-related disorders.
