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Receptor tyrosine kinases and cancer: oncogenic mechanisms and therapeutic approaches

Oncogene volume 40, pages 4079–4093 (2021)Cite this article

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Abstract

Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease, notably cancer. Since their discovery, several mechanisms of RTK dysregulation have been identified, resulting in multiple cancer types displaying ‘oncogenic addiction’ to RTKs. As a result, RTKs have represented a major class for targeted therapeutics over the past two decades, with numerous small molecule-based tyrosine kinase inhibitor (TKI) therapeutics having been developed and clinically approved for several cancers. However, many of the current RTK inhibitor treatments eventually result in the rapid development of acquired resistance and subsequent tumor relapse. Recent technological advances and tools are being generated for the identification of novel RTK small molecule therapeutics. These newer technologies will be important for the identification of diverse types of RTK inhibitors, targeting both the receptors themselves as well as key cellular factors that play important roles in the RTK signaling cascade.

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Fig. 1: Overview of general RTK architecture and signaling pathways.
Fig. 2: Mechanisms of RTK hyperactivation and dysregulation.
Fig. 3: Emerging RTK drug discovery technologies.
Fig. 4: Small molecule approaches to targeting RTK signalling.
Fig. 5: Model of basic organization of RTK endocytic pathway.

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Authors and Affiliations

  1. Drug Discovery Program, Ontario Institute for Cancer Research, Toronto, ON, Canada

    Punit Saraon

  2. Donnelly Centre, University of Toronto, Toronto, ON, Canada

    Shivanthy Pathmanathan, Jamie Snider, Anna Lyakisheva, Victoria Wong & Igor Stagljar

  3. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

    Shivanthy Pathmanathan & Igor Stagljar

  4. Department of Biochemistry, University of Toronto, Toronto, ON, Canada

    Igor Stagljar

  5. Mediterranean Institute for Life Sciences, Split, Croatia

    Igor Stagljar

  6. School of Medicine, University of Split, Split, Croatia

    Igor Stagljar

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  1. Punit Saraon
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  2. Shivanthy Pathmanathan
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  4. Anna Lyakisheva
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  5. Victoria Wong
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Correspondence to Igor Stagljar.

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Saraon, P., Pathmanathan, S., Snider, J. et al. Receptor tyrosine kinases and cancer: oncogenic mechanisms and therapeutic approaches. Oncogene 40, 4079–4093 (2021). https://doi.org/10.1038/s41388-021-01841-2

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  • DOI: https://doi.org/10.1038/s41388-021-01841-2

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