Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

E-Poster Display

1736P - Elevated AXL expression following SARS-CoV-2 infection in non-small cell lung cancer


17 Sep 2020


E-Poster Display


Kavya Ramkumar


Annals of Oncology (2020) 31 (suppl_4): S934-S973. 10.1016/annonc/annonc289


K. Ramkumar1, C..A. Stewart1, C. Gay1, R. Cardnell1, L. Diao2, Q. Wang2, L. Shen2, Y. Xi2, S. Kundu1, C. Della Corte3, D. Gibbons1, J. Wang2, J.V. Heymach1, L.A. Byers1

Author affiliations

  • 1 Department Of Thoracic/head And Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 2 Department Of Bioinformatics And Computational Biology, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 3 Department Of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples/IT


Abstract 1736P


Patients with thoracic cancers affected by the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appear to have poor clinical outcomes. AXL, a TAM (Tyro3, AXL, Mer) family receptor tyrosine kinase, is a known mediator of epithelial to mesenchymal transition (EMT) and therapeutic resistance in non-small cell lung cancer (NSCLC) and other cancers. Additionally, AXL plays a role in efficient Ebola and Zika viral entry and infection and AXL inhibition has demonstrated antiviral activities. 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.


We analyzed mRNA expression of AXL and other TAM family members as well as angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, in treatment-naïve (n=1016) and previously treated (n=239) NSCLC tumors and in a panel of NSCLC cell lines (n=70). We also analyzed AXL mRNA levels in NSCLC cell lines (n=3) infected with SARS-CoV-2.


In treatment-naïve and previously-treated NSCLC tumors, AXL mRNA expression was higher in mesenchymal tumors, as expected, and inversely correlated with ACE2. Similarly, in NSCLC cell lines, high ACE2 expression was associated with low AXL mRNA and protein expression. Notably, expression of ACE2 was downregulated while that of AXL and ZEB1, an EMT transcription factor, were upregulated in NSCLC cells infected with SARS-CoV-2 as compared to mock infected cells, suggesting a shift to a more mesenchymal phenotype. Treatment with bemcentinib for 24h downregulated ZEB1 expression in mesenchymal cell lines, reversing EMT.


These data, in the context of ACE2’s role in preventing acute respiratory distress syndrome, suggest a shift from ACE2-expressing epithelial cells to a more mesenchymal phenotype characterized by low ACE2 and high AXL expression, upon infection of NSCLC cells with SARS-CoV-2. In addition to bemcentinib’s antiviral activity, it can also reverse EMT, further supporting AXL and EMT as novel therapeutic targets for COVID-19 treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Lauren A. Byers.


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.).


C. Gay: Research grant/Funding (self): AstraZeneca. D. Gibbons: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (self): Janssen; Research grant/Funding (self): Takeda; Research grant/Funding (self): Ribon Therapeutics; Research grant/Funding (self): Astellas. J.V. Heymach: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Genentech; Advisory/Consultancy, Research grant/Funding (self): GlaxoSmithKline; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Hengrui; Advisory/Consultancy: Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (self), Licensing/Royalties: Spectrum; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Synta; Research grant/Funding (self): Bayer. L.A. Byers: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; AbbVie; GenMab; Sierra Oncology; Advisory/Consultancy: BergenBio; Pharma Mar SA; Merck; Bristol Myers Squibb; Genentech; Pfizer; Research grant/Funding (self): Tolero Pharmaceuticals. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.