Pharmacokinetic Acceleration via CYP3A4 Hyperactivation as a Clinically Actionable Mechanism of Targeted Therapy Resistance in NSCLC
Pragya Kumar, Menkara Henry, Julia Pelesko, Bina Desai, Malgorzata Tyczynska Weh, Ramu Kakumanu, Min Liu, Natália Souza Nunes Siqueira, Robert Vander Velde, Viktoriya Marusyk, Jyllica Aurelio, Eric B. Haura, Jhanelle Gray, Bruna Pellini, David Basanta, Andriy Marusyk
This paper identifies CYP3A4 hyperactivation as a tumor-extrinsic resistance mechanism in NSCLC, showing it reduces drug exposure and leads to resistance, and proposes dosing optimization and CYP3A4 inhibition as solutions.
bioRxiv · May 20, 2026 · PreprintCancer Biology