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BIOMARKER:

AXL expression

i
Other names: AXL Receptor Tyrosine Kinase, Tyrosine Protein Kinase Receptor UFO, AXL Oncogene, AXL Transforming Sequence Gene, Tyro7
Entrez ID:
Related biomarkers:
3d
Integrated proteomics-based physical and functional mapping of AXL kinase signaling pathways and inhibitors define its role in cell migration. (PubMed, Mol Cancer Res)
Comparison of three AXL inhibitors reveals that TKI RXDX-106 inhibits pAXL, pAKT and migration/invasion of these cells without reducing their viability, while Bemcentinib exerts AXL-independent phenotypic effects on viability...However, a unique vulnerability was identified in one resistant clone, wherein combination of Bemcentinib and Erlotinib inhibited cell viability and signaling...Cell lines have a wide range of AXL expression, with basal activation detected rarely. Implications: Our study defines mechanisms of action of AXL in lung cancers which can be used to establish assays to measure drug targetable active AXL-complexes in patient tissues and inform the strategy for targeting it's signaling as an anticancer therapy.
Journal
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EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase)
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AXL overexpression • AXL expression
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erlotinib • bemcentinib (BGB324) • RXDX-106
6d
SKI-G-801, an AXL kinase inhibitor, blocks metastasis through inducing anti-tumor immune responses and potentiates anti-PD-1 therapy in mouse cancer models. (PubMed, Clin Transl Immunology)
SKI-G-801 significantly suppressed tumor metastasis and growth by enhancing anti-tumor immune responses. Our results suggest that SKI-G-801 has the potential to overcome anti-PD-1 therapy resistance and allow more patients to benefit from anti-PD-1 therapy.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • AXL (AXL Receptor Tyrosine Kinase)
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AXL expression
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SKI-G-801
13d
Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis. (PubMed, EBioMedicine)
sAXL appears as a biomarker for early detection of PDAC and PDAC-CP discrimination that could accelerate treatment and improve its dismal prognosis.
Journal
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AXL (AXL Receptor Tyrosine Kinase) • GAS6 (Growth arrest specific 6) • Cancer antigen 19-9
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AXL expression
20d
AXL Knock-Out in SNU475 Hepatocellular Carcinoma Cells Provides Evidence for Lethal Effect Associated with G2 Arrest and Polyploidization. (PubMed, Int J Mol Sci)
Pharmacological inhibition of AXL by R428 recapitulated G2 arrest and polyploidy phenotype. These observations strongly suggest that acute loss of AXL in some mesenchymal HCC cells is lethal and points out that its inhibition may represent a druggable vulnerability in AXL-high HCC patients.
Journal
|
AXL (AXL Receptor Tyrosine Kinase)
|
AXL expression
|
bemcentinib (BGB324)
1m
AXL targeting by a specific small molecule or monoclonal antibody inhibits renal cell carcinoma progression in an orthotopic mice model. (PubMed, Physiol Rep)
Remarkably, their in vivo antitumor effectiveness was not significantly enhanced by concomitant administration of a multi-target tyrosine kinase inhibitor. Bemcentinib and tilvestamab qualify as compounds of potentially high clinical interest in AXL overexpressing RCC.
Preclinical • Journal
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AXL (AXL Receptor Tyrosine Kinase) • GAS6 (Growth arrest specific 6) • VIM (Vimentin)
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AXL overexpression • AXL expression • VIM expression
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bemcentinib (BGB324) • tilvestamab (BGB149)
2ms
Prognostic value and immunological role of AXL gene in clear cell renal cell carcinoma associated with identifying LncRNA/RBP/AXL mRNA networks. (PubMed, Cancer Cell Int)
AXL was revealed to play prognostic and immunological roles in ccRCC and LncRNA/RBP/AXL mRNA axes were also identified by us for its potential mechanisms.
Journal • Tumor Mutational Burden
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TMB (Tumor Mutational Burden) • AXL (AXL Receptor Tyrosine Kinase) • CA9 (Carbonic anhydrase 9)
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AXL overexpression • AXL expression • VEGFA elevation • TP53 expression
2ms
INTERIM SAFETY AND EFFICACY RESULTS FROM A PHASE 1/2 STUDY OF BA3011, A CAB-AXL-ADC, IN PATIENTS WITH ADVANCED SARCOMA OR OTHER SOLID TUMORS (CTOS 2021)
Based on preliminary efficacy and safety results from this study, the benefit-risk profile of BA3011 monotherapy appears to be favorable in subjects with sarcoma. No clinically meaningful on-target toxicity was observed. In Phase 1 sarcoma subjects, evidence of antitumor activity was observed, with higher AXL tumor membrane expression correlating with response.
Clinical • P1/2 data • PD(L)-1 Biomarker • IO biomarker
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AXL (AXL Receptor Tyrosine Kinase)
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AXL expression
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mecbotamab vedotin (BA3011)
2ms
AXL AS A POTENTIAL THERAPEUTIC TARGET FOR SOFT TISSUE SARCOMA (CTOS 2021)
All experiments ended for individual mice either when the tumor volume exceeded 500 or 1000 mm3, when the tumor showed ulceration, in case of serious clinical illness, when the tumor growth blocked the movement of the mouse, or when tumor growth assessment had been completed.Treatments with BGB324 was carried out for 72h and readout was performed with Cell Titer Blue according to manufacturers instruction... We wanted to use relevant pre-clinical sarcoma models, which constitute an important challenge within the sarcoma field. Thus far, we have successfully transplanted 2 sarcoma murine cell lines with relevant histologies according to our pathologists. In one of this cell lines, we show that AXL KO cells present a growth disadvantage in vivo compared to their WT counterparts.
PD(L)-1 Biomarker • IO biomarker
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BRAF (B-raf proto-oncogene) • PD-L1 (Programmed death ligand 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • AXL (AXL Receptor Tyrosine Kinase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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CDKN2A deletion • AXL expression • AXL-L
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bemcentinib (BGB324)
2ms
RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study. (PubMed, Front Oncol)
A final logistic regression analysis showed Breslow and AXL-positive immunoreactivity as the stronger predictor for positive sentinel node status [area under the receiver operating characteristic curve (AUC) of 0.96]. AXL could be a potential new biomarker for MM risk assessment, and it deserves to be further investigated in larger studies.
Clinical • Journal
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AXL (AXL Receptor Tyrosine Kinase) • RIPK3 (Receptor Interacting Serine/Threonine Kinase 3)
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AXL expression • AXL positive
2ms
NSAIDs Sensitize Melanoma Cells to MEK Inhibition and Inhibit Metastasis and Relapse by Inducing Degradation of AXL. (PubMed, Pigment Cell Melanoma Res)
Furthermore, NSAIDs not only sensitized the MEK inhibitor treatment, but also reduced EMT and relapse mediate by AXL in tumor tissue. Our findings suggest that the combination of inhibitors and NSAIDs, especially Aspirin, could be a simple but efficient modality to treat melanoma in which AXL is a key factor for drug-resistance, metastasis, and relapse.
Journal
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HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
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AXL expression
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aspirin
3ms
ARE STEM CELL MARKER EXPRESSION AND CD133 ANALYSIS RELEVANT TO DIFFERENTIATE COLORECTAL CANCER? (PubMed, Arq Bras Cir Dig)
CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AXL (AXL Receptor Tyrosine Kinase) • CD133
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MYC expression • AXL expression • CD133 positive • CD33 positive • CD133 expression
3ms
Obesity-associated leptin promotes chemoresistance in colorectal cancer through YAP-dependent AXL upregulation. (PubMed, Am J Cancer Res)
Therefore, the aim of this study was to clarify the role of leptin and the underlying mechanisms in mediating 5-fluorouracil (5-FU) resistance in CRC...Furthermore, leptin neutralization rescued the sensitivity of CRC tumors to 5-FU in mice fed on a high-fat diet (HFD). These results indicated that leptin mediated 5-FU resistance through YAP-dependent AXL overexpression in CRC.
Journal
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AXL (AXL Receptor Tyrosine Kinase) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1)
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AXL overexpression • AXL expression
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5-fluorouracil
3ms
Gas6/Axl signaling pathway promotes proliferation, migration and invasion and inhibits apoptosis in A549 cells. (PubMed, Exp Ther Med)
Recombinant human Gas6 protein and inhibitor TP-0903 were used to activate and inhibit the Gas6/Axl signaling pathway, respectively...Activity of Gas6/Axl signaling pathway was shown to be positively associated with cell proliferation by Cell Counting Kit 8 and clone formation assays. In conclusion, the Gas6/Axl signaling pathway was revealed to promote the proliferation, migration and invasion and inhibit the apoptosis of lung adenocarcinoma cells, which serve important roles in the progression of lung adenocarcinoma.
Journal
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CASP3 (Caspase 3) • CASP8 (Caspase 8) • GAS6 (Growth arrest specific 6) • CASP9 (Caspase 9) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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AXL expression
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dubermatinib (TP-0903)
4ms
An evolving role for AXL in metastatic renal cell carcinoma. (PubMed, Clin Cancer Res)
High tumoral expression of AXL was associated with inferior response to anti-PD-1 therapy and increased tumoral PD-L1 expression in patients with metastatic renal cell carcinoma, with particularly poor outcomes in those with high AXL and PD-L1. AXL expression has potential as a biomarker and therapeutic target.
Journal • PD(L)-1 Biomarker • IO biomarker
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AXL (AXL Receptor Tyrosine Kinase)
|
PD-L1 expression • AXL expression
4ms
Molecular characterization of AXL in solid tumor malignancies using real-world data (SITC 2021)
Conclusions Analyses of real-world mRNA datasets showed that AXL was upregulated in specific tumor and treatment settings as well as in patient populations with specific mutations and disease subtypes. Findings here should be validated with independent datasets.
Clinical • Real-world evidence • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ARID1A (AT-rich interaction domain 1A) • AXL (AXL Receptor Tyrosine Kinase) • KDM6A (Lysine Demethylase 6A)
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PD-L1 expression • KRAS mutation • ARID1A mutation • AXL expression
5ms
Association of AXL and PD-L1 expression with clinical outcomes in patients with advanced renal cell carcinoma treated with PD-1 blockade. (PubMed, Clin Cancer Res)
Our findings propose AXL as candidate factor of resistance to PD-1 blockade, and provide compelling support for screening both AXL and PD-L1 expression in the management of advanced ccRCC.
Clinical • Clinical data • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • AXL (AXL Receptor Tyrosine Kinase) • CD163 (CD163 Molecule)
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PD-L1 expression • PD-L1 overexpression • VHL mutation • AXL expression • MS4A1 mutation
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Opdivo (nivolumab)
7ms
AXL Overexpression in Tumor-Derived Endothelial Cells Promotes Vessel Metastasis in Patients With Hepatocellular Carcinoma. (PubMed, Front Oncol)
R428 reduced tumor growth and CD 31 expression in HCC in PDX xenograft nude mice. Therefore, AXL over-expression in TECs promotes vessel metastasis of HCC, which indicates that AXL in TECs could be a potential therapeutic target in HCC patients with PVTT.
Clinical • Journal
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AXL (AXL Receptor Tyrosine Kinase) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • SOX2
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DKK1 overexpression • AXL overexpression • AXL expression
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bemcentinib (BGB324)
7ms
AXL inhibition in macrophages stimulates host-versus-leukemia immunity and eradicates naive and treatment resistant leukemia. (PubMed, Cancer Discov)
Remarkably, AXL deficiency in macrophages also enables PD1 checkpoint blockade in PD1-refractory leukemias. Lastly, we provide proof-of-concept that a clinical grade AXL inhibitor can be used in combination with standard of care therapy to cure established leukemia, regardless on AXL expression in malignant cells.
Journal • PD(L)-1 Biomarker • IO biomarker
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GAS6 (Growth arrest specific 6)
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AXL expression
8ms
AXL is crucial for E1A-enhanced therapeutic efficiency of EGFR tyrosine kinase inhibitors through NFI in breast cancer. (PubMed, Environ Toxicol)
NFI-C and NFI-X, not NFI-A and NFI-B, resulting in cell death in response to EGFR-TKI. Our finding suggests that NFI-C and NFI-X are crucial regulators for AXL and significantly correlated with poor survival of breast cancer patients.
Journal
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EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase) • NFIB (Nuclear Factor I B)
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AXL expression
9ms
ARE STEM CELL MARKER EXPRESSION AND CD133 ANALYSIS RELEVANT TO DIFFERENTIATE COLORECTAL CANCER? (PubMed, Arq Bras Cir Dig)
CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AXL (AXL Receptor Tyrosine Kinase) • CD133
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MYC expression • AXL expression • CD133 positive • CD33 positive • CD133 expression
10ms
AXL is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. (PubMed, Mol Cancer Res)
We demonstrate that AXL-deficiency extends survival, reduces primary and metastatic burden and enhances sensitivity to gemcitabine in an autochthonous model of PDA...Finally, we demonstrate that AXL-positive poorly differentiated tumor cells are critical for PDA progression and metastasis, emphasizing the potential of AXL as a therapeutic target in PDA. Implications: These studies implicate AXL as a marker of undifferentiated PDA cells and a target for therapy.
Journal
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AXL (AXL Receptor Tyrosine Kinase) • MERTK (MER Proto-Oncogene, Tyrosine Kinase)
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AXL expression
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gemcitabine
10ms
[VIRTUAL] Longitudinal AXL assessment of circulating tumor cells (CTCs) and its clinical implication in the patients with EGFR mutated non-small cell lung cancer (NSCLC) (AACR 2021)
Gefitinib for EGFR mutated non-small cell lung cancer (NSCLC) is showing acquired resistance after 8-11 months, and about 60% of its mechanisms have been reported due to T790M mutation...Conclusively, this study implicates that AXL in CTCs could be deployed for prognostic evaluation. And the clinical monitoring of specific target marker in CTC could help for further treatment strategy.
Clinical • Circulating Tumor Cells
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EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase)
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EGFR mutation • EGFR T790M • AXL expression
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gefitinib
11ms
Clinical
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AXL (AXL Receptor Tyrosine Kinase)
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EGFR mutation • EGFR expression • AXL expression
12ms
Cooperative targeting of immunotherapy-resistant melanoma and lung cancer by an AXL-targeting antibody-drug conjugate and immune checkpoint blockade. (PubMed, Cancer Res)
Here we show that enapotamab vedotin (EnaV), an antibody-drug conjugate (ADC) targeting AXL, effectively targets tumors that display insensitivity to immunotherapy or tumor-specific T cells in several melanoma and lung cancer models...Combining EnaV with tumor-specific T cells proved superior to either treatment alone in models of melanoma and lung cancer and induced ICB benefit in models otherwise insensitive to anti-PD-1 treatment. Our findings indicate that targeting AXL-expressing, immunotherapy-resistant tumors with EnaV causes an immune-stimulating tumor microenvironment and enhances sensitivity to ICB, warranting further investigation of this treatment combination.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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AXL (AXL Receptor Tyrosine Kinase)
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AXL expression
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enapotamab vedotin (HuMax-AXL-ADC)
1year
Transcriptional activators YAP/TAZ and AXL orchestrate dedifferentiation, cell fate, and metastasis in human osteosarcoma. (PubMed, Cancer Gene Ther)
Collectively, we present a laboratory-based method to detect and characterize a pure population of dCTCs, which provides a unique opportunity to study how OS cell fate and differentiation contributes to metastatic potential. Though the important step of clinical validation remains, our identification of AXL, ZEB1, and TWIST upregulation raises the tantalizing prospect that EMT-TF-directed therapies might expand the arsenal of therapies used to combat advanced-stage OS.
Journal
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AXL (AXL Receptor Tyrosine Kinase) • SOX9 (SRY-Box Transcription Factor 9) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
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AXL expression
1year
MicroRNA 34a-AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells. (PubMed, Genes (Basel))
Finally, the overexpression of microRNA-34a (miR-34a), which is a well-described EMT-inhibiting miRNA and targets AXL, inhibited VM formation, migration, and invasion in MDA-MB 231 cells. These results identify a miR-34a-AXL axis that is critical for the regulation of VM formation and may serve as a therapeutic target to inhibit tumor neovascularization.
Journal
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AXL (AXL Receptor Tyrosine Kinase) • MIR34A (MicroRNA 34a-5p)
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AXL overexpression • AXL expression
1year
Comprehensive analysis of 34 MiT family translocation renal cell carcinomas and review of the literature: investigating prognostic markers and therapy targets. (PubMed, Pathology)
Larger tumour size, the presence of necrosis and MET immunohistochemical expression correlate with aggressive behaviour in Xp11 renal cell carcinomas, especially in combination. VEGF, MET, cathepsin K but not AXL may be potential predictive markers for targeted therapy in MiT family translocation renal cell carcinomas.
Review • Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • AXL (AXL Receptor Tyrosine Kinase) • CA9 (Carbonic anhydrase 9) • CD68 (CD68 Molecule)
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MET amplification • AXL expression • CA9 expression
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Cabometyx (cabozantinib tablet)
1year
[VIRTUAL] Phase 1 Study of the AXL Inhibitor DS-1205 in Combination With Osimertinib in Subjects With Metastatic or Unresectable EGFR-Mutant NSCLC (IASLC-WCLC 2020)
Eligible subjects must either have evidence of radiological disease progression during treatment with erlotinib, gefitinib, or afatinib without the T790M resistance mutation, or must experience disease progression during osimertinib treatment and no risk factors for QTc prolongation. Preliminary analysis of efficacy data reveals that three patients had stable disease beyond 100 days (RECIST v.1.1). Conclusion Dose escalation is ongoing and updated clinical and biomarker data will be presented.
Clinical • P1 data • Combination therapy
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M • AXL expression • EGFR T790M negative
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erlotinib • Gilotrif (afatinib) • Tagrisso (osimertinib) • gefitinib • AB-329
1year
AXL Inhibition Enhances MEK Inhibitor Sensitivity in Malignant Peripheral Nerve Sheath Tumors. (PubMed, J Cancer Sci Clin Ther)
Together these findings suggest that AXL inhibition enhances the sensitivity of MPNST to other small molecule inhibitors. We conclude that combination therapy with AXL inhibitor may be a therapeutic option for MPNST.
Journal
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GAS6 (Growth arrest specific 6)
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AXL expression
1year
Axl and Mertk receptors cooperate to promote breast cancer progression by combined oncogenic signaling and evasion of host anti-tumor immunity. (PubMed, Cancer Res)
The anti-tumor activity from Mertk inhibition was abrogated by depletion of cytotoxic CD8α T cells by using anti-CD8α mAb or by transplantation of tumor cells into B6.CB17-Prkdc SCID mice. Our data indicate that targeting Axl expressed on tumor cells and Mertk in the tumor microenvironment are predicted to have a combinatorial benefit to enhance current immunotherapies and that Axl and Mertk have distinct functional activities that impair host anti-tumor response.
Journal • PD(L)-1 Biomarker
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AXL (AXL Receptor Tyrosine Kinase) • MERTK (MER Proto-Oncogene, Tyrosine Kinase)
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AXL expression • MERTK expression
1year
TGFβ promotes YAP-dependent AXL induction in mesenchymal-type lung cancer cells. (PubMed, Mol Oncol)
Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal-type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP-dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal-type lung cancer.
Journal
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AXL (AXL Receptor Tyrosine Kinase) • SMAD4 (SMAD family member 4)
|
AXL expression
|
doxorubicin hydrochloride
1year
[VIRTUAL] Axl-RTK Inhibition Modulates Monocyte Immune Response to Enhance the Anti-Tumor Effects of CD19 Redirected Chimeric Antigen Receptor T Cells in Preclinical Models (ASH 2020)
In summary, Axl-RTK inhibition with TP-0903 demonstrates a direct suppression of inhibitory monocytes, which in turn enhances CART cell function. Our findings support the strategy of further refining and testing the novel and potent combination of Axl-RTK inhibition and CART cell therapy for the treatment of B cell malignancies.
Preclinical • CAR T-Cell Therapy • IO biomarker
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CD19 (CD19 Molecule) • AXL (AXL Receptor Tyrosine Kinase) • IL6 (Interleukin 6) • CD14 • IL17A (Interleukin 17A) • CD40LG (CD40 ligand) • IL1B (Interleukin 1, beta)
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AXL overexpression • AXL expression
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dubermatinib (TP-0903)
1year
BRN2 and MITF together impact AXL expression in melanoma. (PubMed, Exp Dermatol)
Further, re-expression of BRN2 led to decreased AXL expression, indicating a role for BRN2 in regulation of AXL levels unrelated to effects on MITF level. As AXL has been recognized as a marker of therapy resistance these cells may represent a population of cells responsible for disease relapse and as potential targets for therapeutic treatment.
Journal
|
AXL (AXL Receptor Tyrosine Kinase) • MITF (Melanocyte Inducing Transcription Factor)
|
AXL overexpression • AXL expression
1year
AXL Is a Driver of Stemness in Normal Mammary Gland and Breast Cancer. (PubMed, iScience)
An AXL-dependent gene signature is a feature of transcriptomes in basal breast cancers and reduced patient survival irrespective of subtype. Our interpretation is that AXL regulates access to epithelial plasticity programs in MaSCs and, when co-opted, maintains acquired stemness in breast cancer cells.
Journal
|
AXL (AXL Receptor Tyrosine Kinase)
|
AXL expression
1year
[VIRTUAL] Identification of soluble AXL as a potential non-invasive serum biomarker for glioblastoma (SNO 2020)
Though sAXL shed from brain tumors is detectable in the serum of GBM patients, in this small series of patients, it does not correlate with tumor volume. That said, we feel a larger study correlating sAXL level with improved volumetric MRI determination of viable GBM is warranted.
AXL (AXL Receptor Tyrosine Kinase)
|
AXL expression
1year
Hematopoietic progenitor kinase 1 down-regulates the oncogenic receptor tyrosine kinase AXL in pancreatic cancer. (PubMed, J Biol Chem)
Our results suggest that HPK1 is a tumor suppressor that targets AXL for degradation via the endocytic pathway. HPK1 loss of function may contribute to AXL overexpression and thereby enhance AXL-dependent downstream signaling and tumor invasion in PDAC.
Journal
|
AXL (AXL Receptor Tyrosine Kinase) • CBL (Cbl proto-oncogene) • GAS6 (Growth arrest specific 6)
|
AXL overexpression • AXL expression
over1year
Clinical
|
EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase)
|
EGFR mutation • EGFR L858R • EGFR overexpression • AXL overexpression • AXL expression
|
Tagrisso (osimertinib)
over1year
[VIRTUAL] Impact of pretreatment AXL expression on osimertinib efficacy in patients with nonsmall cell lung cancer with EGFR mutation (ESMO Asia 2020)
The maximal tumor shrinkage rate following osimertinib treatment in the patients with AXL expression scores of 0 and 1+ was higher than that in patients with AXL expression scores of 2+ and 3+ (44.12% vs. 25.93%, p = 0.094). Pre-treatment AXL expression in tumors may be a promising predictor of osimertinib treatment efficacy in patients with EGFR-mutated NSCLC.
Clinical
|
EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase)
|
EGFR mutation • EGFR L858R • EGFR overexpression • AXL overexpression • AXL expression
|
Tagrisso (osimertinib)
over1year
[VIRTUAL] Impact of pretreatment AXL expression on osimertinib efficacy in patients with nonsmall cell lung cancer with EGFR mutation (ESMO Asia 2020)
The maximal tumor shrinkage rate following osimertinib treatment in the patients with AXL expression scores of 0 and 1+ was higher than that in patients with AXL expression scores of 2+ and 3+ (44.12% vs. 25.93%, p = 0.094). Pre-treatment AXL expression in tumors may be a promising predictor of osimertinib treatment efficacy in patients with EGFR-mutated NSCLC.
Clinical
|
EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase)
|
EGFR mutation • EGFR L858R • EGFR overexpression • AXL overexpression • AXL expression
|
Tagrisso (osimertinib)
over1year
AXL Inactivation Inhibits Mesothelioma Growth and Migration via Regulation of p53 Expression. (PubMed, Cancers (Basel))
AXL inhibition (shRNA or R428) reduced mesothelioma cell viability, migration, and invasion, whereas TP53 shRNA knockdown attenuated antiproliferative, migration, and invasive effects of AXL silencing or AXL inactivation in these cells. These studies demonstrate a novel feedback regulation loop between AXL and p53, and provide a rationale for mesothelioma therapies targeting AXL/p53 signaling.
Journal
|
AXL (AXL Receptor Tyrosine Kinase) • GAS6 (Growth arrest specific 6)
|
TP53 mutation • AXL expression • TP53 expression
|
bemcentinib (BGB324)
over1year
The crosstalk between AXL and YAP promotes tumor progression through STAT3 activation in head and neck squamous cell carcinoma. (PubMed, Cancer Sci)
Mechanistically, Gas6 induced a competitive binding to phosphorylated signal transducers and activators of transcription 3 (STAT3) with large tumor suppressor kinase 1 (LATS1) and inhibited the Hippo pathway. This study revealed a novel non-transcriptional effect of STAT3 in Gas6/AXL-induced YAP activity, suggesting that STAT3 acted as a critical "molecular switch" during the mutual promotion between AXL and YAP, which might be a promising therapeutic target in HNSCC.
Journal
|
AXL (AXL Receptor Tyrosine Kinase) • STAT3 (Signal Transducer And Activator Of Transcription 3) • GAS6 (Growth arrest specific 6)
|
AXL overexpression • AXL expression • GAS6 overexpression
over1year
Co-overexpression of AXL and c-ABL predicts a poor prognosis in esophageal adenocarcinoma and promotes cancer cell survival. (PubMed, J Cancer)
We demonstrated that the pro-survival activity of AXL requires c-ABL expression in response to serum deprivation. This study highlights the importance of the co-overexpression of AXL and c-ABL proteins as a valuable prognostic biomarker and targeting these proteins could be an effective therapeutic approach in EAC or other solid tumors expressing high levels of AXL and c-ABL proteins.
Journal
|
ABL1 (ABL proto-oncogene 1) • AXL (AXL Receptor Tyrosine Kinase)
|
AXL overexpression • AXL expression
over1year
The actin modulator hMENA regulates GAS6-AXL axis and pro-tumor cancer/stromal cell cooperation. (PubMed, EMBO Rep)
Clinically, we found that a high hMENA/GAS6/AXL gene expression signature is associated with a poor prognosis in PDAC and NSCLC. We propose that hMENA contributes to cancer progression through paracrine tumor-stroma crosstalk, with far-reaching prognostic and therapeutic implications for NSCLC and PDAC.
Journal
|
AXL (AXL Receptor Tyrosine Kinase) • GAS6 (Growth arrest specific 6)
|
AXL overexpression • AXL expression
over1year
AXL targeting overcomes human lung cancer cell resistance to NK and CTL-mediated cytotoxicity. (PubMed, Cancer Immunol Res)
Higher ICAM1 and ULBP1 tumor expression correlated with improved patient survival in two NSCLC cohorts. These results reveal an AXL-mediated immune escape regulatory pathway, suggest AXL as a candidate biomarker for tumor resistance to NK and CTL immunity, and support AXL targeting to optimize immune response in NSCLC.
Journal
|
AXL (AXL Receptor Tyrosine Kinase) • ICAM1 (Intercellular adhesion molecule 1)
|
AXL expression
over1year
Long non-coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL. (PubMed, J Cell Mol Med)
Collectively, our data identified LINC00526 as a tumour suppressor in glioma via forming a double negative feedback loop with AXL. Our data also suggested LINC00526 as a potential prognostic biomarker and therapeutic candidate for glioma.
Journal
|
EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • AXL (AXL Receptor Tyrosine Kinase)
|
AXL expression
over1year
AXL is a predictor of poor survival and of resistance to anti-EGFR therapy in RAS wild-type metastatic colorectal cancer. (PubMed, Eur J Cancer)
AXL is a marker of poor prognosis in mCRC with consistent clinical and preclinical evidences of involvement in primary and acquired resistance to anti-EGFR drugs in RAS WT patients.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • AXL (AXL Receptor Tyrosine Kinase)
|
KRAS exon 2 mutation • AXL overexpression • AXL expression
|
Erbitux (cetuximab)
over1year
Cetuximab in Head and Neck Cancer Patients (clinicaltrials.gov)
P2, N=36, Recruiting, University of Wisconsin, Madison | Suspended --> Recruiting
Clinical • Enrollment open
|
AXL (AXL Receptor Tyrosine Kinase)
|
AXL expression
|
Erbitux (cetuximab)
over1year
Axl and autophagy LC3 expression in tumors is strongly associated with clinical prognosis of hepatocellular carcinoma patients after curative resection. (PubMed, Cancer Med)
High Axl expression in tumors is associated with aggressive tumor behavior and worse clinical outcomes. Furthermore, the combination of high Axl and low LC3 expression significantly predicts poorer prognosis for HCC patients who underwent hepatectomy.
Clinical • Journal
|
AXL (AXL Receptor Tyrosine Kinase)
|
AXL expression
over1year
Tumor tissue and plasma levels of AXL and GAS6 before and after tyrosine kinase inhibitor treatment in EGFR-mutated non-small cell lung cancer. (PubMed, Thorac Cancer)
Plasma concentrations of AXL and GAS6 do not reflect tumor expression levels, and their measurement is thus not a viable alternative to direct analysis of tumor tissue in EGFR-mutated NSCLC.
Journal
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EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase) • GAS6 (Growth arrest specific 6)
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EGFR mutation • AXL expression
over1year
[VIRTUAL] Elevated AXL expression following SARS-CoV-2 infection in non-small cell lung cancer (ESMO 2020)
Recently, bemcentinib, a highly selective and potent AXL inhibitor with antiviral activity, has been fast-tracked as the first potential treatment for assessment in the United Kingdom’s ACcelerating COVID-19 Research & Development (ACCORD) multicenter, randomized phase II trial...Funding: NIH/NCI CCSG P30-CA016672 (Bioinformatics Shared Resource), NIH/NCI T32 CA009666, ASCO Young Investigator Award (C.M.G.); University of Texas SPORE in Lung Cancer P5-CA070907 (L.A.B. C.M.G.), NIH/NCI R01-CA207295, NIH/NCI U01-CA213273, the Department of Defense (LC170171) (L.A.B.), The LUNGevity foundation (D.G., L.A.B.), through generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shot Program (J.V.H., J.W., L.A.B.); an Andrew Sabin Family Fellowship (L.A.B.), and The Rexanna Foundation for Fighting Lung Cancer (J.V.H., L.A.B.).
AXL (AXL Receptor Tyrosine Kinase) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
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AXL expression • ZEB1 expression
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bemcentinib (BGB324)
over1year
[VIRTUAL] Exploring the correlation between AXL expression and gene expression molecular subtyping (GEMS) in high grade serous ovarian cancer (HGSOC) (ESMO 2020)
Sensitivity to the AXL kinase inhibitor, bemcentinib (BerGenBio), has been demonstrated in-vitro for C1 subtype HGSOC (Antony et al 2018). Positive AXL expression has been associated with improved progression-free survival (PFS) in lung cancer patients treated with bemcetinib and pembrolizumab (Krebs et al SITC 2019, CT03184571)...Legal entity responsible for the study: The authors. Funding: BerGenBio, NMRC/CTGIITE/0004/2016.
PD(L)-1 Biomarker
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AXL (AXL Receptor Tyrosine Kinase)
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AXL expression
|
Keytruda (pembrolizumab) • bemcentinib (BGB324)
over1year
Clinical • P1 data • Combination therapy
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M • AXL expression • EGFR mutation + EGFR T790M • EGFR T790M negative
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gefitinib • AB-329
over1year
Exosome-transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma. (PubMed, Cancer Med)
AXL-associated exosomal linc00852 up-regulated the proliferation, migration, and invasion of osteosarcoma cells, which would be considered as a new tumor biomarker and a special therapeutic target for osteosarcoma.
Journal
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AXL (AXL Receptor Tyrosine Kinase)
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AXL expression
over1year
MicroRNA-34a inhibits cell invasion and epithelial-mesenchymal transition via targeting AXL/PI3K/AKT/Snail signaling in nasopharyngeal carcinoma. (PubMed, Genes Genomics)
Our results demonstrate that miR-34a/AXL can inhibit NPC cell migration, invasion and EMT through inhibition of AKT/Snail signaling.
Journal
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AXL (AXL Receptor Tyrosine Kinase) • CDH1 (Cadherin 1) • VIM (Vimentin)
|
AXL overexpression • AXL expression • CDH1 expression • VIM expression
over1year
Hematopoietic niche drives FLT3-ITD acute myeloid leukemia resistance to quizartinib via STAT5- and hypoxia- dependent up-regulation of AXL. (PubMed, Haematologica)
These data highlight a new bypass mechanism specific to the hematopoietic niche that hampers the response to quizartinib through combined up-regulation of AXL activity. Targeting this signaling offers the prospect of a new therapy to eradicate resistant FLT3-ITD leukemic cells hidden within their specific microenvironment, thereby preventing relapses from FLT3-ITD clones.
Journal
|
FLT3 (Fms-related tyrosine kinase 3) • NTRK (Neurotrophic receptor tyrosine kinase)
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FLT3-ITD mutation • AXL expression
|
Vanflyta (quizartinib)
over1year
Implications of the Receptor Tyrosine Kinase Axl in Gastric Cancer Progression. (PubMed, Onco Targets Ther)
Mechanistic investigations revealed that Axl promoted EMT, invasion, and proliferation via upregulating ZEB1 expression in GC cells. Our results demonstrated that the Gas6/Axl/ZEB1 signaling pathway regulated EMT, invasion, and proliferation in GC cells and might represent a potential therapeutic target for GC treatment.
Journal
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AXL (AXL Receptor Tyrosine Kinase) • GAS6 (Growth arrest specific 6) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
|
AXL overexpression • AXL expression • ZEB1 expression
over1year
Synergistic effect of the inhibitors of RAF/MEK and AXL on KRAS-mutated ovarian cancer cells with high AXL expression. (PubMed, Cancer Sci)
We found that CH5126766 and R428 suppressed the phosphorylation of ERK and AKT, respectively, and their combination synergistically inhibited the growth of both cell lines with enhancement of apoptosis accompanied by the Bim up-regulation. Combined treatment with CH5126766 and R428 is expected as the novel therapeutic option for KRAS-mutated ovarian cancer with high expression of AXL.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • AXL (AXL Receptor Tyrosine Kinase)
|
KRAS mutation • AXL overexpression • AXL expression • KRAS expression
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VS-6766 • bemcentinib (BGB324)
over1year
Cytoplasmic Expression of AXL Is Associated With High Risk of Postoperative Relapse of Conventional Renal Cell Carcinoma. (PubMed, Anticancer Res)
Detecting cytoplasmic expression of AXL can be used to define a subset of conventional RCC with high risk of progression, thus identifying patients for more aggressive surveillance and adjuvant AXL inhibitor treatment as early as possible.
Journal
|
AXL (AXL Receptor Tyrosine Kinase)
|
AXL expression
over1year
Qigesan inhibits esophageal cancer cell invasion and migration by inhibiting Gas6/Axl-induced epithelial-mesenchymal transition. (PubMed, Aging (Albany NY))
Moreover, QGS decreased Gas6/Axl levels, increased E-cadherin expression, decreased Snail and N-cadherin expression, and inhibited epithelial-mesenchymal transition (EMT) in EC cells. QGS thus suppresses EMT in EC by inhibiting Gas6/Axl binding.
Journal
|
CDH1 (Cadherin 1) • GAS6 (Growth arrest specific 6)
|
AXL expression • CDH1 expression
over1year
[VIRTUAL] Uncovering Intra-tumor AXL Expression Heterogeneity and Outcomes in Clear Cell Renal Cell Carcinoma: Comprehensive Analysis for Primary and Metastatic lesion. (AUA 2020)
We revealed intra-tumor AXL expression heterogeneity, and spatial AXL expression levels affects OS in ccRCC. The levels of AXL expression was increased in metastases, and site-specific differences of AXL expression levels were evident. Our study may depict potential candidates for clinically targeting AXL e.g., Cabozantinib treatments in ccRCC.
AXL (AXL Receptor Tyrosine Kinase)
|
AXL expression
|
Cabometyx (cabozantinib tablet)
over1year
[VIRTUAL] In vivo efficacy and safety of RGX-019, a MerTK targeting monoclonal antibody (AACR-II 2020)
Additionally, no clinical hematologic toxicities were observed. Pro-inflammatory macrophage-related cytokines were detected in the plasma after RGX-019 dosing, confirming target engagement in vivo.The MOA and safety profile of RGX-019, along with its high selectivity, affinity, in vivo efficacy, and immunologic activity, support further advancement of RGX-019 as a clinical candidate for development in solid and liquid cancers.
Late-breaking abstract
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AXL (AXL Receptor Tyrosine Kinase) • MERTK (MER Proto-Oncogene, Tyrosine Kinase) • GAS6 (Growth arrest specific 6)
|
AXL overexpression • AXL expression • MERTK expression
|
RGX-019
over1year
[VIRTUAL] Novel mechanism involved in the regulation ofoncogenic Axl receptor tyrosine kinase in cancer (AACR-II 2020)
Our results suggest a novel tumor suppressor mechanism of HPK1 in which it targets Axl for degradation via the endocytic pathway. Loss of HPK1 may contribute to Axl overexpression and enhance its downstream signaling and tumor invasion in pancreatic cancer.
AXL (AXL Receptor Tyrosine Kinase) • CBL (Cbl proto-oncogene) • GAS6 (Growth arrest specific 6)
|
AXL overexpression • AXL expression
over1year
[VIRTUAL] Identifying the role of AXL in fusion kinase inhibitor resistant non-small cell lung cancer (AACR-II 2020)
Combining the AXL inhibitor R428 with TKI treatment, such as crizotinib for ALK and ROS1 driven cell lines, was effective at inhibiting colony formation and wound healing in fusion kinase inhibitor resistant cell lines. In a RET inhibitor resistant model expression of both AXL and EGFR are elevated and the receptors interact, which can be disrupted upon EGF stimulation, to drive resistance. Collectively, we show that AXL upregulation is a common marker of TKI resistance among ALK, ROS1, and RET fusion kinase driven lung adenocarcinoma models, and provide rationale for AXL as a clinical target for combination therapy to overcome drug resistance.
ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • AXL (AXL Receptor Tyrosine Kinase) • VIM (Vimentin)
|
RET fusion • ALK rearrangement • AXL expression • VIM expression
|
Xalkori (crizotinib) • bemcentinib (BGB324)
over1year
[VIRTUAL] Pharmacological inhibition of AXL with BGB324 sensitizes HCC cells to sorafenib treatment and promotes an immunostimulatory microenvironment (AACR-II 2020)
Taken together, our current data suggests sorafenib resistant HCC cells to regulate the immune microenvironment via AXL and lactate modulation. Combination treatment of sorafenib and BGB324 may represent a novel therapeutic approach to combat HCC.
PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1)
|
AXL expression
|
Nexavar (sorafenib) • bemcentinib (BGB324)
over1year
Role of the receptor tyrosine kinase AXL in regulating antitumor response and relationship with hypoxic stress (IMMUNOLOGY 2020)
Using a cohort of 324 metastatic RCC patients treated with anti-PD1, we could demonstrate that AXL expression may interfere with the clinical outcome. The relationship between VHL dysfunction, AXL expression and patient response to anti-PD1 will be discussed.
PD(L)-1 Biomarker • IO biomarker
|
AXL (AXL Receptor Tyrosine Kinase) • VHL (von Hippel-Lindau tumor suppressor) • NKG2D (killer cell lectin like receptor K1) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
|
VHL mutation • AXL expression • ZEB1 expression
over1year
Targeting AXL-JAK1 in tumor and immune ecosystem of lung cancer (IMMUNOLOGY 2020)
Moreover, pSTAT3 expression levels were increased in U937 differentiated macrophage after co-culture with A549 cells. This novel platform may facilitate the optimal selection of lung cancer patients for dual targeting of AXL and JAK1-pSTAT3 in the future.
AXL (AXL Receptor Tyrosine Kinase) • JAK1 (Janus Kinase 1) • JAK3 (Janus Kinase 3)
|
AXL overexpression • AXL expression
almost2years
Molecular Signatures for Combined Targeted Treatments in Diffuse Malignant Peritoneal Mesothelioma. (PubMed, Int J Mol Sci)
Mutations in MET Sema domain were exclusively found in two "progressed" DMPMs, and the combined Axl and MET inhibition reduced cellular motility in a DMPM cell line obtained from a "progressed" DMPM. Conclusion-The results indicate that the coordinated activity of multiple cross-talks between RTKs is directly involved in the biology of DMPM, suggesting the combined inhibition of PIK3 and mTOR as an effective strategy that may be easily implemented in clinical practice, and indicating that the combined inhibition of EGFR/HER2 and HER3 and of Axl and MET deserves further investigation.
Journal
|
EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase)
|
HER-2 expression • EGFR expression • AXL expression