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Project Information
Project Title:  Organoids to guide Post-resistance Therapy In driver MutAted Lung cancers (OPTIMAL)
Period:  from: 2020-10-01 to: 2025-09-30  
Principal Investigator(s): Liu, Geoffrey  
Co-Investigators: Arrowsmith, Cheryl H ; Haibe-Kains, Benjamin ; Lupien, Mathieu ; Moran, Michael Francis ; Pugh, Trevor John ; Radulovich, Nikolina ; Tsao, Ming-Sound  
Supervisors:  
Previous Investigators/Supervisors:  
Institution: University Health Network (Toronto)  
Department: Medical Biophysics 
Program: Project Grant 
Assigned PRC: CPT 
Primary Institute: Cancer Research 
Primary Theme: Biomedical 
Keywords: ANAPLASTIC LYMPHOMA KINASE REARRANGEMENTS, DRUG RESISTANCE MECHANISMS, DRUG SENSITIVITY SCREENING, EPIDERMAL GROWTH FACTOR RECEPTOR, EPIGENETICS, GENOMICS, NON-SMALL CELL LUNG CANCER, PATIENT-DERIVED ORGANOIDS, ROS1 REARRANGEMENTS, TRASCRIPTOMICS 
Abstract: Some types of lung cancer can be specifically targeted by "designer" drugs. Most patients initially respond very well to these targeted drugs with prolonged survival, but eventually they grow resistant and stop responding. Determining which drug to offer next is a major challenge. We have developed a novel model to study drug resistance: 3-dimensional Patient-Derived cancer cell clusters, or "Organoids" (PDOs). PDOs can be rapidly grown from patient biopsies, mimic important properties of patient tumours and are amenable to laboratory characterization. We hypothesize that extensive drug testing and molecular profiling of PDOs can help scientists identify new effective treatments and help doctors to make better treatment decisions for lung cancer patients. We have already shown that our PDO models successfully mirror their original tumours. Our first aim is to optimize PDO model generation and drug testing. Our second aim is to test our PDO model system in patients: we will biopsy patients when their tumours stop responding to a targeted drug and grow these biopsies as PDOs. We will then test a series of clinically-available drugs on these models to determine the most effective treatment for each patient. Tracking the molecular changes in these models will show us how these drugs are working (or not working). Our third aim will explore the use of experimental drug compounds on PDO models to discover new agents for lung cancer therapy. The results of this study have the potential to greatly impact the management of lung cancer: 15% of lung cancers (>4000/year in Canada) are targetable, mostly in younger patients who have never smoked. Targeted therapies have the potential to convert currently fatal cancer into chronic, controllable and manageable disease. The major barrier to this promise is drug resistance. Our research will identify novel resistance mechanisms and methods to overcome this resistance, providing a clinical pipeline to personalize cancer therapy. 

Funding Information
Fiscal Year Amount
2020-21 $114,750