2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03F.03 Utility of Patient-Derived Xenograft and Xenograft-Derived Organoid Models with EGFR Mutation to Study EGFR-TKI Resistance.

P1.03F.03 Utility of Patient-Derived Xenograft and Xenograft-Derived Organoid Models with EGFR Mutation to Study EGFR-TKI Resistance.

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The study conducted by researchers from Princess Margaret Cancer Centre focuses on the challenge of resistance to tyrosine kinase inhibitors (TKIs), such as osimertinib, in treating lung adenocarcinoma (LUAD) with mutations in the epidermal growth factor receptor (EGFR). The researchers developed patient-derived xenografts (PDXs) and their corresponding xenograft-derived organoids (XDOs) from patients with both treatment-naïve and TKI-resistant LUAD. These models were evaluated for their accuracy in reflecting clinical responses to TKIs and their utility in facilitating new drug screenings.<br /><br />The study established 22 PDX and 13 paired XDO models with varied EGFR-TKI sensitivities. The results demonstrated that the responses of these models were largely concordant with clinical responses, validating their use as research tools. The models also revealed genetic alterations associated with resistance mechanisms to osimertinib, suggesting that they have the potential to provide insights into overcoming drug resistance.<br /><br />Additionally, high-throughput drug screening is in progress using these models, which could lead to the discovery of new therapeutic strategies to counteract resistance to osimertinib and other EGFR-TKIs. This research underscores the importance of using complex genetic and response models to study drug resistance and advance the development of more effective treatments for lung adenocarcinoma patients with EGFR mutations. Overall, PDX and XDO models offer a promising platform for further investigations into combating acquired resistance in cancer therapy.

Asset Subtitle

Nhu-An Pham

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Speaker Nhu-An Pham

Topic Tumor Biology – Translational Biology

Keywords

lung adenocarcinoma

tyrosine kinase inhibitors

osimertinib resistance

EGFR mutations

patient-derived xenografts

xenograft-derived organoids

drug screening

cancer therapy

genetic alterations

Princess Margaret Cancer Centre