Development of small molecule inhibitors and antibodies targeting AXL for tumor therapy and infectious disease control

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About this Research Topic

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Background

Cancer and infectious diseases are regulated by immune responses. In terms of immune regulation, the AXL pathway has a pivotal role in the pathogenesis and development of cancer. AXL is expressed on the immune cells and cancer, and has emerged as a key facilitator of immune escape, and has been related to anti-cancer drug resistance. In addition, infection with viruses such as ZIKA virus, SARS virus and RSV is facilitated/mediated by the Gas6/AXL pathway. AXL-targeting small molecular inhibitors and antibodies have been developed as anti-cancer drugs, to be likely applied in combination with current immunotherapies and chemo- and radiotherapy. AXL targeting drugs are also being considered as a new concept in the control of infectious diseases. In this perspective, a more thorough and comprehensive immune-biological analysis of the anti-cancer and anti-infective effects of AXL targeting drugs is urgently needed.

This Research Topic, therefore aims to assemble a series of Original Research and Review articles introducing the biological and immunological mechanisms of AXL molecules and pathways in health and disease and addressing the clinical development of AXL targeting drugs.

1. Molecular structure of the AXL molecule and inhibitor binding mechanisms
-Investigating the extracellular domains of AXL and its structural homologies to better understand heterodimerization and signaling.

2. Homeostatic mechanism of the phosphatidylserine-GAS6-AXL axis
-Investigating the natural homeostatic roles of the PtdSer-GAS6-AXL axis to understand the function of the normal AXL molecule and its relation to immunosuppressive mechanisms
-Defects of TAM family and the relation between natural homeostatic mechanisms and drug toxicity

3. Metastasis and AXL: comprehensive bioinformatics views.
-Understanding the AXL mutation and correlation between EMT genes and tumor-associated immune deconvolution

4. EGFR, ALK and BRAF targeting inhibitors and AXL-mediated resistance mechanisms.
-Investigating targeted therapy resistance mechanisms reported with AXL overexpression
-Potential effects of combination therapy with AXL inhibitors.

5. Immune evasion mechanisms and AXL
-Describing the complex networks between immune cells and cancer cells to understand the AXL mechanisms at the basis of immune evasion.

6. Clinical development of AXL inhibitors: antibodies and small molecules
-Illustrating the AXL inhibitor or antibody development
-Toxicity and PK/PD of AXL inhibitors
-Preclinical studies with AXL inhibitors and AXL targeting antibodies

7. AXL as biomarker for infectious diseases and novel drug-target to cease pathogenicity
-sAXL (soluble AXL) as a potential biomarker in infectious disease progression (in terms of both viral and bacterial infection)
-AXL-mediated infections (AXL promotes infection of Zika and Ebola Virus)
-AXL- binding drug candidates for ameliorating primary pathology of infectious diseases

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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