Molecular drivers and therapeutic targets for neuroendocrine transformation in lung cancer
Triparna Sen, PhD, Memorial Sloan Kettering Cancer Center, New York, NY, talks on an investigation into molecular drivers and therapeutic targets for neuroendocrine transformation in lung cancer. EGFR-mutant adenocarcinoma transforms into small cell lung cancer (SCLC) as a mechanism of resistance to tyrosine kinase inhibitors (TKIs). A mutliomic analysis was conducted on combined histology tumors, whereby the lung adenocarcinoma and SCLC components were in the same spatial region. Microdissection of samples were performed and analyzed via various platforms, including Whole Exome Sequencing (WES), bulk RNA-sequencing, methylation analysis and immunohistochemistry. Via WES, p53 and RB1 loss were found in almost all combined histology tumors. Via bulk RNA-Seq, NOTCH inhibition and upregulation of several PCR2 complexes and DNA damage response genes were shown to be predictors of transformation. Additionally, AKT inhibition demonstrated to be an effective therapeutic target in a mutant mouse model. Notably, the addition of osimertinib to AKT inhibition performed better in mouse models than either agent alone. This interview took place at the IASLC 2022 World Conference on Lung Cancer congress in Vienna, Austria.
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