Assistant Research Professor Houston Methodist Research Institute Houston, Texas
We explore the use of multiscale mechanistic models to bridge preclinical and clinical stages of cancer therapy development. Focusing on non-small-cell lung cancer, we study how elevated microRNA-155 (miR-155) influences cisplatin resistance and anti-tumor immunity. We developed a multiscale model characterizing pharmacokinetics/pharmacodynamics, intratumoral transport phenomena, and tumor-immune interactions to simulate treatment with nanoparticle-delivered anti-miR-155. Our model, calibrated with in vivo data and extrapolated to humans, evaluates the clinical efficacy of anti-miR-155 therapy. Simulations in virtual patient cohorts reveal that combination of anti-miR-155 with standard-of-care drugs significantly improve progression-free survival (PFS) compared to monotherapies. Specifically, combining anti-miR-155 with cisplatin or pembrolizumab yields synergistic effects, with a three-drug regimen achieving a median PFS of 13.1 months. This approach also highlights the importance of optimizing dosage regimens to avoid antagonistic effects. Our findings underscore the potential of multiscale modeling in supporting the clinical translation of novel anti-cancer therapies and advancing personalized medicine.
Learning Objectives:
Understand the role of miR-155 in NSCLC treatment: Attendees will learn about the dual role of microRNA-155 in promoting drug resistance and boosting anti-tumor immunity, and its implications for treatment outcomes in non-small-cell lung cancer.
Explore translational modeling in drug combination strategies: Participants will gain insights into how multiscale mechanistic modeling, combined with preclinical and clinical data, can be used to predict the efficacy of anti-miR-155 therapies alone and in combination with standard-of-care drugs like cisplatin and pembrolizumab.
Optimize combination therapies for NSCLC: The session will highlight strategies for designing synergistic drug combinations, focusing on dose optimization to maximize efficacy and minimize antagonistic effects, with the goal of improving progression-free survival in NSCLC patients.
