RAS: Striking at the Core of the Oncogenic Circuitry
Open accessAbstract
Cancer is a devastating disease process that touches the lives of millions worldwide. Despite advances in our understanding of the genomic architecture of cancers and the mechanisms that underlie cancer development, a great therapeutic challenge remains. Here, we revisit the birthplace of cancer biology and review how one of the first discovered oncogenes, RAS, drives cancers in new and unexpected ways. As our understanding of oncogenic signaling has evolved, it is clear that RAS signaling is not homogenous, but activates distinct downstream effectors in different cancer types and grades. RAS signaling is tightly controlled through a series of post-transcriptional mechanisms, which are frequently distorted in the context of cancer, and establish key metabolic and immunologic states that support cancer growth, migration, survival, metastasis, and plasticity. While targeting RAS has been fiercely pursued for decades, new strategies have recently emerged with the potential for therapeutic efficacy. Thus, understanding the complexities of RAS biology may translate into improved therapies for patients with RAS-driven cancers.
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RAS pathway abnormalities, including activating RAS mutations, are common across many cancer types.
“abnormalities in components of the RAS pathway, including activating RAS mutations, are common across a diverse range of malignancies”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [3]
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Reconstruction and analysis of a large-scale binary Ras-effector signaling network
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Clinical and Genomic Landscape of RAS Mutations in Gynecologic Cancers
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STK19 is a DNA/RNA-binding protein critical for DNA damage repair and cell proliferation
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Targeting KRAS in NSCLC: Old Failures and New Options for “Non-G12c” Patients
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Conquering oncogenic KRAS and its bypass mechanisms
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Peptide inhibitors: Breaking cancer code
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Targeting Ras with protein engineering
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The complex journey of targeting RAS in oncology
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The miRNome of canine invasive urothelial carcinoma
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Single cell spatial biology over developmental time can decipher pediatric brain pathologies
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Recent advances in therapeutic targeting of the KRAS pathway in cancer
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Ras-mediated activation of mTORC2 promotes breast epithelial cell migration and invasion
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Phakomatoses and Endocrine Gland Tumors: Noteworthy and (Not so) Rare Associations
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Transcriptome Changes in Glioma Cells Cultivated under Conditions of Neurosphere Formation
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CTP synthase: the hissing of the cellular serpent
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Neuroepithelial cell competition triggers loss of cellular juvenescence
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Oncogenic mutations of KRAS modulate its turnover by the CUL3/LZTR1 E3 ligase complex
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Effects of constitutively active K-Ras on axon regeneration after optic nerve injury
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HPLC Method to Resolve, Identify and Quantify Guanine Nucleotides Bound to the GTPase Ras
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SARS-CoV-2 Vaccination and the Multi-Hit Hypothesis of Oncogenesis
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Lactate Oxidase Disrupts Lactate-Activated RAS and PI3K Oncogenic Signaling
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Studying early structural changes in SOS1 mediated KRAS activation mechanism
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New Developments in Treating RAS-Mutated Metastatic Colorectal Cancer
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Enhanced proliferation in a prawn embryonic primary cell culture ectopically expressing mutated Ras
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Natural Chalcones and Their Derivatives Target the Tumor Microenvironment in Colon Cancer
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Parallels between oncogene-driven cardiac hyperplasia and heart regeneration in zebrafish
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Exploiting KRAS-mediated metabolic reprogramming as a therapeutic target
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- Authors
- Gimple, R. C., & Wang, X.
- Affiliations
- University of California San Diego (US)
- Nanjing Medical University (CN)
- Corresponding author
- Wang, Xiuxing
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2019-09-24
- Volume
- 9
- Pages
- 965-965
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC6798062
- OpenAlex
- W2976175424
- Cited by
- 174
- References
- 162
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 30 · 2023: 38 · 2022: 34 · 2021: 29 · 2020: 7
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Servier
- National Institutes of Health
- National Cancer Institute (F30CA217065)
- National Institute of General Medical Sciences (T32GM007250)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- Ras, oncogenes, Ras signaling, post-transcriptional regulation, RAS-driven cancers, cancer metabolism, tumor immunology, metastasis, tumor plasticity, RAS-targeted therapy
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