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Liver Cancer in the Middle East pp 333–364Cite as

Targeting c-Met and AXL Crosstalk for the Treatment of Hepatocellular Carcinoma

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Abstract

Recently, efforts in developing effective therapeutics for unresectable hepatocellular carcinoma (HCC) focused on systemic therapy by means of multikinase and immune checkpoint inhibition. However, a desirable response has not yet been achieved in HCC treatment due to rapid development of resistance against systemic therapeutics. Receptor crosstalk, a key mechanism in drug resistance, enables ligand-independent activation of receptor tyrosine kinases (RTKs). c-Met and AXL are members of the RTK family, both well-known for heterodimerizing with other RTKs causing aberrant signaling, aggressive character, and therapy resistance. A large body of preclinical and clinical data suggested correlations between c-Met and AXL in expression and activation in tumors, upregulating migration and invasion. Co-targeting these receptors is promising and has shown to enable improvements in antitumor efficacy of several therapy methods. HCC patients with elevated expression and activation of c-Met and AXL would benefit from dual inhibition that limits this crosstalk and allows to overcome therapy resistance. In this book chapter, we provide an overview of the role of c-Met and Axl signaling in HCC and share our experience and view on scientific rationale for targeting crosstalk between these two RTKs for the treatment of HCC.

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Author notes

  1. Yeliz Yılmaz, Tuğçe Batur and Peyda Korhan contributed equally with all other contributors.

Authors and Affiliations

  1. Cancer Biology and Signaling Group, Basic and Translational Research Program, Izmir Biomedicine and Genome Center, Izmir, Turkey

    Yeliz Yılmaz, Peyda Korhan & Neşe Atabey

  2. Cancer Mechanism and Theranostics Group, Technological Research Program, Izmir Biomedicine and Genome Center, Izmir, Turkey

    Tuğçe Batur & Mehmet Öztürk

  3. Department of Medical Biology, Faculty of Medicine, Izmir Tinaztepe University, Buca, Izmir, Turkey

    Mehmet Öztürk & Neşe Atabey

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  1. Yeliz Yılmaz
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  2. Tuğçe Batur
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  3. Peyda Korhan
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  4. Mehmet Öztürk
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  5. Neşe Atabey
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Corresponding author

Correspondence to Neşe Atabey .

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Editors and Affiliations

  1. Translational HCC Research, Liver Transplantation Institute, Inonu University, Malatya, Turkey

    Brian I. Carr

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Yılmaz, Y., Batur, T., Korhan, P., Öztürk, M., Atabey, N. (2021). Targeting c-Met and AXL Crosstalk for the Treatment of Hepatocellular Carcinoma. In: Carr, B.I. (eds) Liver Cancer in the Middle East. Springer, Cham. https://doi.org/10.1007/978-3-030-78737-0_21

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  • DOI: https://doi.org/10.1007/978-3-030-78737-0_21

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