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Prospects of current AXL-targeting therapies in early phase cancer trials
Juhye Yim1, Chloe Hope1, Justus M Huelse1
1Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, GA, USA.
Introduction:
AXL, a member of the TAM (TYRO3, AXL, and MERTK) family of receptor tyrosine kinases, controls pro-tumorigenic signaling cascades and cancer-immunological functions, and promotes drug resistance. Due to AXL's multifaceted role and therapeutic activity in preclinical studies, a variety of AXL inhibitors are being developed and tested in clinical trials for cancer treatment. Some clinical studies are showing promising results for AXL inhibitors as monotherapy and in combination with standard of care therapeutics. Currently, no selective AXL-targeting therapy has reached FDA-approval, but several compounds have entered phase II and III studies.
Area Covered:
We elaborate on the role of AXL in cancer progression and suppressing anti-cancer immunity at both the molecular level and immune cell interaction level. Additionally, we review pre-clinical and clinical data of AXL-targeting agents.
Expert Opinion:
Preclinical and several early clinical trials demonstrated the safety of AXL-targeting monotherapies with some evidence of efficacy. Additionally, multiple novel combination regimens including AXL-targeting agents to overcome resistance mechanisms are being actively examined with some promising results. However, patient selection and companion biomarkers may be critical for the success of AXL-targeting therapies.
Insights
AXL receptor tyrosine kinase inhibitors show promise in cancer treatment, with ongoing trials exploring their efficacy alone and in combination therapies. Patient selection and biomarkers are key to successful AXL-targeted treatments.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- AXL, a receptor tyrosine kinase, plays a key role in cancer progression, immune suppression, and drug resistance.
- Targeting AXL is a promising strategy for cancer therapy, with several inhibitors in development.
Purpose of the Study:
- To review the role of AXL in cancer and anti-cancer immunity.
- To summarize preclinical and clinical data on AXL-targeting agents.
Main Methods:
- Review of preclinical studies on AXL inhibitors.
- Analysis of early-phase clinical trial data for AXL-targeting monotherapies and combination regimens.
Main Results:
- AXL inhibitors demonstrate safety and some efficacy as monotherapies in early clinical trials.
- Combination therapies involving AXL inhibitors show promise in overcoming resistance mechanisms.
Conclusions:
- AXL-targeting therapies are under active investigation for cancer treatment.
- Patient selection and companion biomarkers are crucial for the success of AXL-targeted therapies.
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