First evidence of AXL expression on circulating tumor cells in metastatic breast cancer patients: A proof‐of‐concept study

Abstract

BackgroundFor several years, the AXL tyrosine kinase receptor, a member of the Tyro3‐Axl‐Mer (TAM) family, has been considered a new strategic target in oncology. AXL overexpression is common in solid tumors and is associated with poor prognosis. In this context, the detection of a subset of circulating tumor cells (CTCs) that express AXL (AXL+ CTCs) could be clinically relevant.MethodsImmunostaining was performed to assess AXL expression in human breast cancer cell lines. The optimal conditions were established using flow cytometry. Spiking experiments were carried out to optimize the parameters of the CellSearch® system detection test. CTC enumeration and AXL expression were evaluated in patients with metastatic breast cancer (mBC) before treatment initiation.ResultsAn innovative AXL+ CTC detection assay to be used with the CellSearch® system was developed. In a prospective longitudinal clinical trial, blood samples from 60 patients with untreated mBC were analyzed to detect AXL+ CTCs with this new assay. CTCs were detected in 35/60 patients (58.3%) and AXL+ CTCs were identified in 7 of these 35 patients (11.7% of all patients).ConclusionThis newly established AXL+ CTC assay is a promising tool that can be used for liquid biopsy in future clinical trials to stratify and monitor patients with cancer receiving anti‐AXL therapies.

Targeting Tyro3, Axl, and MerTK Receptor Tyrosine Kinases Significantly Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibition

“…High Met activity is a known driver of carcinogenesis, tumor growth, and treatment resistance with shortened survival in breast cancer [ 64 ]. TAM RTKs have recently been implicated in tumor growth, metastasis, and therapeutic resistance in breast cancer [ 19 , 20 , 21 , 22 , 23 ]. Furthermore, the TAM receptors also promote the creation of an immunosuppressive TME [ 24 , 25 , 26 , 27 ], thereby constituting an attractive therapeutic target.…”

“…The TAM (Tyro3, Axl, and MerTK) family of receptor tyrosine kinases (RTKs) has recently been implicated in tumor growth, metastasis, and therapeutic resistance in breast cancer [ 19 , 20 , 21 , 22 , 23 ]. Given their high expression in immune cells, the TAM receptors also play crucial roles in promoting immune evasion and the creation of an immunosuppressive tumor microenvironment (TME) [ 24 , 25 , 26 , 27 ], thereby constituting an attractive therapeutic target.…”