Gene of the month:Axl

Abstract

The interaction between Axl receptor tyrosine kinase and its main ligand Gas6 has been implicated in the progression of a wide number of malignancies. More recently, overexpression of Axl has emerged as a key molecular determinant underlying the development of acquired resistance to targeted anticancer agents. The activation of Axl is overexpression-dependent and controls a number of hallmarks of cancer progression including proliferation, migration, resistance to apoptosis and survival through a complex network of intracellular second messengers. Axl has been noted to influence clinically meaningful end points including metastatic recurrence and survival in the vast majority of tumour types. With Axl inhibitors having gained momentum as novel anticancer therapies, we provide an overview of the biological and clinical relevance of this molecular pathway, outlining the main directions of research.

Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors

“…AXL (previously known as UFO ), is a member of the TMA ( TYRO3 , MER , and AXL ) receptor tyrosine kinase family and has important roles in various cancer processes [reviewed in ref. 41]. AXL amplification has been identified in colorectal cancer 42 Moreover, AXL overexpression has been observed in many solid and hematopoietic malignancies, including Ewing sarcoma tumor tissues 43 and sarcoma cell lines 44 .…”

Transcriptional upregulation of c‐MYC by AXL confers epirubicin resistance in esophageal adenocarcinoma

“…A previous report indicated that the increasing overexpression of AXL was associated with Barrett's carcinogenesis, and could be used as an adverse prognostic marker in EAC (Hector et al, 2010). The increasing knowledge on the role of AXL in regulating several aspects of cancer has justified a growing interest in the development and clinical testing of AXL inhibitors for targeted therapies (reviewed in Brown et al, 2016;Gay et al, 2017;Levin et al, 2016). An early study demonstrated that AXL mediates the acquired resistance to EGFR-targeted therapy in lung cancer (Zhang et al, 2012).…”

Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinib

“…Our report, represents the first association of AXL positivity by immunohistochemistry with reduced survival in patients with mRCC treated with sunitinib. AXL has been suggested to promote both intrinsic and acquired resistance to different treatments, from chemotherapy to molecular targets [15]. In RCC xenograft models upregulation of AXL and MET showed resistance to longterm sunitinib therapy, as well as resensitisation to sunitinib after AXL and MET inhibition via treatment with the TKI cabozantinib [34].…”

“…Remarkable efforts are being made to identify biomarkers that may predict response to select and treat more effectively patients with metastatic RCC (mRCC) [14]. AXL, a gene that encodes a receptor tyrosine kinase, is involved with a wide variety of cancerous hallmarks such as proliferation, survival, evasion from apoptosis, enhanced angiogenesis, and invasiveness [15,16]. Recently, AXL have been suggested as a biomarker of poor prognosis and a potential target for different types of cancers [17,18], including RCC [19,20].…”