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Review
. 2021 Mar 25;13(7):1521.
doi: 10.3390/cancers13071521.

The Role of the Receptor Tyrosine Kinase Axl in Carcinogenesis and Development of Therapeutic Resistance: An Overview of Molecular Mechanisms and Future Applications

Martha Wium  1 , Aderonke F Ajayi-Smith  1 , Juliano D Paccez  2 , Luiz F Zerbini  1
Affiliations
Review

The Role of the Receptor Tyrosine Kinase Axl in Carcinogenesis and Development of Therapeutic Resistance: An Overview of Molecular Mechanisms and Future Applications

Martha Wium et al. Cancers (Basel). .

Abstract

Resistance to chemotherapeutic agents by cancer cells has remained a major obstacle in the successful treatment of various cancers. Numerous factors such as DNA damage repair, cell death inhibition, epithelial-mesenchymal transition, and evasion of apoptosis have all been implicated in the promotion of chemoresistance. The receptor tyrosine kinase Axl, a member of the TAM family (which includes TYRO3 and MER), plays an important role in the regulation of cellular processes such as proliferation, motility, survival, and immunologic response. The overexpression of Axl is reported in several solid and hematological malignancies, including non-small cell lung, prostate, breast, liver and gastric cancers, and acute myeloid leukaemia. The overexpression of Axl is associated with poor prognosis and the development of resistance to therapy. Reports show that Axl overexpression confers drug resistance in lung cancer and advances the emergence of tolerant cells. Axl is, therefore, an important candidate as a prognostic biomarker and target for anticancer therapies. In this review, we discuss the consequence of Axl upregulation in cancers, provide evidence for its role in cancer progression and the development of drug resistance. We will also discuss the therapeutic potential of Axl in the treatment of cancer.

Keywords: Axl; cancer; drug resistance; molecular mechanisms; receptor tyrosine kinase; targeted therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of Axl and its downstream signalling pathways. Various downstream signalling networks can be activated either through the binding of GAS6 (green) to Axl (blue) or through Axl’s interaction with other receptors (yellow).
Figure 2
Figure 2
The role of Axl in resistance to epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2) and HER3 tyrosine kinase inhibitors.
See this image and copyright information in PMC

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