Glioblastoma resistance to EGFR antibody-drug conjugate is driven by transcriptional reprogramming and TEK-induced EGFR suppression
Our findings demonstrate that resistance to ABT-414 arises through both adaptive transcriptional remodeling and newly acquired genetic alterations. TEK-mediated suppression of EGFR represents a previously unrecognized mechanism of resistance, with potential implications for overcoming antibody-drug conjugate failure in GBM.
Authors
- Kendra A. Porath (ORCID: https://orcid.org/0009-0009-0248-0523)
- Jann Nagina Sarkaria (ORCID: https://orcid.org/0000-0001-7489-4885)
- Nhan L. Tran (ORCID: https://orcid.org/0000-0003-0908-9964)
- Fulvio D’Angelo (ORCID: https://orcid.org/0000-0002-4940-4693)
- Dustin Grief
- Teresa Noviello (ORCID: https://orcid.org/0000-0002-3411-6752)
- Ritin Sharma (ORCID: https://orcid.org/0000-0001-8365-9916)
- Shannon P. Fortin Ensign (ORCID: https://orcid.org/0000-0002-7433-528X)
- Benjamin E. Rabichow (ORCID: https://orcid.org/0000-0003-3672-3430)
- Mylan Blomquist
- Jean Kloss (ORCID: https://orcid.org/0000-0003-1640-5777)
- Krystine Garcia‐Mansfield (ORCID: https://orcid.org/0000-0002-9089-2254)
- Antonella Paladino (ORCID: https://orcid.org/0000-0002-9397-1572)
- Antonio Iavarone (ORCID: https://orcid.org/0000-0002-0683-4634)
- Patrick Pirrotte (ORCID: https://orcid.org/0000-0003-1360-6039)
- Michele Ceccarelli (ORCID: https://orcid.org/0000-0002-4702-6617)
- Sonia Jain (ORCID: https://orcid.org/0000-0002-3728-6642)
- Bianca M. Marin (ORCID: https://orcid.org/0000-0001-8534-0378)
- Francesca Pia Caruso (ORCID: https://orcid.org/0000-0002-2206-1459)
- Joseph C. Loftus (ORCID: https://orcid.org/0000-0001-9350-7182)
- Christopher Sereduk
Institutions
- Translational Genomics Research Institute (US)
- University of Miami (US)
- City of Hope (US)
- Biogem (IT)
- Mayo Clinic in Arizona (US)
- Mayo Clinic Hospital (US)
- Institute of Biostructure and Bioimaging (IT)
- National Research Council (IT)
- Sylvester Comprehensive Cancer Center (US)
- Neurological Surgery (US)
Publication Details
- Journal
- Journal of Translational Medicine
- Published
- 2025-10-21
- DOI
- https://doi.org/10.1186/s12967-025-07216-5
- Citations
- 2
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 3.25