Life Sciences & Biotechnology
Title : | Patient derived xenografts for combinatorial therapy of PAK1 and TKI inhibitors as a preclinical platform for EGFR positive NSCLC patients |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. duggirala sridevi, Adyar Cancer Institute, Tamil Nadu |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | duggirala.sri@gmail.com |
Details
Executive Summary : | The development of targeted therapy for lung cancer patients has improved the prognostic outcome, with driver mutations like EGFR/ALK RET ROS leading to the development of new generation of tyrosine kinase inhibitors. Pre-clinical platforms like PDX models are being used to understand the mechanistic role and resistance factors caused by drugs. However, patients with TKI inhibitors targeting EGFR often acquire resistance after 9-12 months of treatment. Combinatorial drugs targeting PAK1 (p21 activated kinase) are needed to improve treatment outcomes. PAK1 overexpression in NSCLC cell line models is independently related to poor survival in patients with NSCLC. PAK1 inhibition in lung cancer cell lines arrests cell cycle in the G1 phase and impairs tumor growth in PDX models. The EGFR pathway is an upstream activator of PAK1, and a combinatorial inhibitor targeting both will be beneficial. This study aims to establish PDX models from surgically resected tissue from NSCLC patients in South India. The PDX models will be treated in combination with novel PAK1 inhibitors and TKI inhibitors. Whole exome sequencing will be used to compare original tissue and PDX tissue, and gene alterations during drug treatment will be analyzed to establish the role of PAK1 in EGFR-positive NSCLC patients. The study proposes a novel combination of PAK1 and EGFR TKI inhibitors as a future treatment strategy for NSCLC. |
Total Budget (INR): | 18,30,000 |
Organizations involved