[C13] Cancer Biology

[C13-04] Treatment Simulation for ALK+ NSCLC: Mathematical Modelling with Drug-Tolerant Persister Cells

*Yoshitaka Kozaki¹, Ryohei Katayama², Shingo Iwami¹ (1. Interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan (Japan), 2. Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan (Japan))

Keywords:

Treatment simulation,Mathematical modeling,ALK-positive Non-Small Cell Lung Cancer,Tumor growth,Resistant mutation,PK/PD model,Persister model,Stochastic simulation

Anaplastic lymphoma kinase-positive non-small cell lung cancer (ALK+ NSCLC) is found in ~3% of patients with lung cancer, the leading cause of cancer-related deaths worldwide. These patients are treated with ALK-tyrosine kinase inhibitors (ALK-TKIs), which have shown high clinical response; however, relapse occurs in most cases, and this is thought to be due to resistance mutations in drug-tolerant persister cells. Here, we developed a treatment simulation of ALK+ NSCLC to search for and evaluate treatment strategies by integrating the pharmacokinetic/pharmacodynamic (PK/PD) analysis of ALK-TKIs and the development of a mathematical model that explains the dynamics of drug-sensitive, -tolerant persister and -resistant cancer cells and using the Gillespie stochastic simulation algorithm. Our studies may lead to the development of optimal therapeutic strategies to overcome acquired resistance to ALK-TKIs.