2023 World Conference on Lung Cancer (Posters)-EP12.02. Judith Tam ALK Lung Cancer Research Initiative

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The Judith Tam ALK Lung Cancer Research Initiative aims to study the mechanisms of resistance to ALK tyrosine kinase inhibitors (TKIs) in patients with ALK-positive non-small cell lung cancer (NSCLC). The initiative collects ALK-positive samples from patients within the Michigan Medicine Health System and other institutions. The project has three main goals:<br /><br />1. Project 1 focuses on drug screening using minimally cultured NSCLC samples obtained at diagnosis, recurrence, or progression. Patient-derived organoids (PDOs) are molecularly characterized to identify therapeutic vulnerabilities and changes throughout the course of the disease.<br /><br />2. Project 2 aims to develop human and murine organoid models to study the early effects of ALK activation on transcription, cell fate, and sensitivity to epigenetic and metabolic inhibitors.<br /><br />3. Project 3 aims to devise new drug combinations targeting ALK and create novel ALK inhibitors. Additionally, there are three developing projects: CTC Analysis Project, Immune Environment Project, and Identification of Novel ALK Inhibitors.<br /><br />The initiative has enrolled 119 distinct patients, with 26 confirmed as ALK-positive, and collected various samples, including tissue, fluid, and blood. PDOs have been established from 7 ALK-positive patients, and drug testing has demonstrated multi-drug resistance in these patients. The screening assay has identified alternative TKIs or chemotherapies with more favorable responses. CTC enrichment and molecular characterization of expanded samples are ongoing. Additionally, 200 compounds designed as proteolysis targeting chimeras (PROTACs) for ALK have been synthesized.<br /><br />The initiative has assembled a multidisciplinary team of experts in genomics, cancer biology, surgery, biomedical engineering, and pharmacology to conduct these projects and develop a better understanding of the molecular mechanisms of resistance and vulnerability in ALK-driven NSCLC. By studying these mechanisms, the initiative aims to guide optimal treatment sequencing for patients and advance the development of novel therapeutics.

Asset Subtitle

Angel Qin

Meta Tag

Speaker Angel Qin

Topic Metastatic NSCLC: Targeted Therapy - FUSIONS

Keywords

ALK tyrosine kinase inhibitors

ALK-positive non-small cell lung cancer

drug screening

patient-derived organoids

therapeutic vulnerabilities

CTC Analysis Project

molecular characterization

multi-drug resistance

proteolysis targeting chimeras (PROTACs)

novel therapeutics