Abstract 669: Dynamic modeling of responses to PDL-1 inhibitors in non-small cell lung cancer: implications for precision combination therapy

Immunotherapy by immune checkpoint blockade has had a promising impact on the treatment of Non-Small Cell Lung Cancer (NSCLC). Although single and combination therapy with checkpoint inhibitors such as PDL-1 inhibitors have been proved to be effective in making the survival of patients with NSCLC longer, but there is always a population of patients which shows resistance to these therapeutic modalities. The source of resistance emerges from signaling pathways and regulatory systems in tumors and the immune system, but the dynamics among tumor components, T cells, and tumor microenvironment contribute in this process as well. To understand the complex system of these interactions, a mathematical model of these pathways and interactions are presented using Ordinary Differential Equations (ODEs). The specific characteristics of NSCLC tumors including metabolic reprogramming have been considered in this model. The model is capable of decoding patient-to-patient variabilities regarding responses to PDL-1 inhibitors, and parameter-sensitivity analysis shows the vulnerable biomarkers to be targeted by combination therapy to give better results in killing the tumor cells. The model can be integrated with PK/PD models to provide an in-silico platform for investigating the therapeutic responses in NSCLC for precision oncology. Note: This abstract was not presented at the meeting. Citation Format: Iman Tavassoly. Dynamic modeling of responses to PDL-1 inhibitors in non-small cell lung cancer: implications for precision combination therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 669.