Feedback and redundancy in receptor tyrosine kinase signaling: relevance to cancer therapies
Abstract
Mammalian cells have multiple regulatory mechanisms to deal with perturbations in cellular homeostasis, including feedback loops and crosstalk between the major signaling pathways. While these mechanisms are critically required to help cells survive under dynamic physiological circumstances, they also pose an impediment to the effective treatment of cancer. In this review, we describe what has been learned about interactions between receptor tyrosine kinase-dependent signaling pathways, and how this knowledge can be used to design rational and more effective combination therapies for cancer.
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Upon K-Ras inhibition, relief of ERK-mediated negative feedback promotes expression of RTKs, which in turn reactivates Ras signaling to confer therapeutic resistance.
“Upon K-Ras inhibition, the relief of ERK-mediated negative feedback promotes the expression of RTKs, which in turn reactivates Ras signaling to confer therapeutic resistance.80,81”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [81]
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References 104 · Cited by 155
- Authors
- Sun, C., & Bernards, R.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Corresponding author
- Bernards, René
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 39
- Issue
- 10
- Pages
- 465-474
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2037720820
- Cited by
- 155
- References
- 104
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 6 · 2023: 14 · 2022: 13 · 2021: 17 · 2020: 20 · 2019: 17 · 2018: 14 · 2017: 18 · 2016: 12 · 2015: 15
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- KWF Kankerbestrijding
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- receptor tyrosine kinase signaling, feedback loops, signaling crosstalk, cancer therapy, combination therapy, drug resistance, cellular homeostasis
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Antineoplastic Agents, Drug Therapy, Combination, Feedback, Humans, Neoplasms, Oncogenes, Signal Transduction, Drug Resistance, Neoplasm, Receptor Protein-Tyrosine Kinases, MAP Kinase Signaling System, raf Kinases, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases, Molecular Targeted Therapy
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