KRAS Oncogenic Signaling Extends beyond Cancer Cells to Orchestrate the Microenvironment
Abstract
KRAS is one of the most frequently mutated oncogenes in cancer, being a potent initiator of tumorigenesis, a strong inductor of malignancy, and a predictive biomarker of response to therapy. Despite the large investment to understand the effects of KRAS activation in cancer cells, pharmacologic targeting of KRAS or its downstream effectors has not yet been successful at the clinical level. Recent studies are now describing new mechanisms of KRAS-induced tumorigenesis by analyzing its effects on the components of the tumor microenvironment. These studies revealed that the activation of KRAS on cancer cells extends to the surrounding microenvironment, affecting the properties and functions of its constituents. Herein, we discuss the most emergent perspectives on the relationship between KRAS-mutant cancer cells and their microenvironment components. Cancer Res; 78(1); 7–14. ©2017 AACR.
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Mutant KRAS has effects on cells of the TME in addition to altering the behaviour of cancer cells themselves.
“Mutant KRAS, like other driver oncogenes, has effects on cells of the TME, in addition to altering the behaviour of cancer cells themselves87,156”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [156]
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References 95 · Cited by 202
- Authors
- Dias Carvalho, P., Guimarães, C. F., Cardoso, A. P., Mendonça, S., Costa, Â. M., Oliveira, M. J., & Velho, S.
- Affiliations
- 1i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
- Universidade do Porto (PT)
- Corresponding author
- Velho, Sérgia
- Venue
- Cancer Research
- Published
- 2018-01-01
- Volume
- 78
- Issue
- 1
- Pages
- 7-14
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2778953850
- Cited by
- 202
- References
- 95
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 28 · 2023: 31 · 2022: 29 · 2021: 32 · 2020: 33 · 2019: 8 · 2018: 7
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundação para a Ciência e a Tecnologia
- European Regional Development Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- KRAS, oncogenic signaling, tumor microenvironment, tumor stromal cells, KRAS-targeted therapy, carcinogenesis, predictive biomarkers
- MeSH terms
- Extracellular Matrix, Fibroblasts, Humans, Mutation, Neoplasms, Genes, ras, Signal Transduction, Tumor Escape, Myeloid Cells, Tumor Microenvironment
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