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

Pdf Summary

The Judith Tam ALK Lung Cancer Research Initiative aims to investigate the mechanisms of resistance in non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene rearrangements. ALK-positive NSCLC tumors typically respond well to ALK tyrosine kinase inhibitors (TKIs), but the development of resistance leads to disease progression. The exact mechanisms of resistance in this type of cancer are not well understood across diverse patient cohorts. The initiative aims to elucidate these mechanisms in order to guide optimal treatment sequencing and develop novel therapeutics.<br /><br />To achieve this objective, the initiative has collected ALK-positive samples, including tumor tissue, blood, and pleural/ascites fluid, from patients within the Michigan Medicine Health System and other institutions through collaborations. A multidisciplinary team of experts in genomics, cancer biology, surgery, engineering, and pharmacology has been assembled to conduct three projects and two developing projects. The projects include drug screening on NSCLC samples, molecular characterization of patient-derived organoids (PDOs) to identify therapeutic vulnerabilities, examination of the early effects of ALK activation using organoid models, development of new drug combinations against ALK, and characterization of circulating tumor cells (CTCs) and the immune environment.<br /><br />Preliminary results show that the initiative has enrolled 91 patients, established PDOs from 7 ALK-positive patients, and collected tissue, fluid, and blood samples. Drug testing has identified alternative TKIs or chemotherapies with more favorable responses in over 50% of cases. CTC enrichment and expansion have been performed, and a patient-derived xenograft (PDX) model has been established. Additionally, 200 compounds called proteolysis targeting chimeras (PROTACs) for ALK have been synthesized.<br /><br />In conclusion, the initiative has developed a workflow to obtain patient samples and assembled an integrative team to study the mechanisms of resistance and vulnerability in ALK-driven NSCLC. The findings from this research could potentially improve treatment outcomes for patients with ALK-positive NSCLC.

Asset Subtitle

Angel Qin

Meta Tag

Speaker Angel Qin

Topic Metastatic NSCLC: Targeted Therapy - FUSIONS

Keywords

Judith Tam ALK Lung Cancer Research Initiative

non-small cell lung cancer

NSCLC

anaplastic lymphoma kinase

ALK gene rearrangements

ALK tyrosine kinase inhibitors

mechanisms of resistance

tumor tissue

patient-derived organoids

circulating tumor cells