ELCC 2022 | Transformed SCLC: characterizing mixed histology tumors

Triparna Sen, PhD, MS, BS, Memorial Sloan Kettering Cancer Center, New York, NY, talks on exploring the characterization of mixed histology tumors via multi-omic platforms, including genomic, transcriptomic and epigenomic. Through whole exome sequencing (WES), universal loss of p53 and RB1 was observed in the transformed component of lung adenocarcinoma. Oncogenic EGFR alterations were also observed in 33% of such cases. Gene expression methylation analysis revealed upregulation of cell cycle progression, DNA repair and chromatin remodeling, as well as suppression of the notch signaling pathway. Transcription factors important for linage switching were noted, as well as the induction of genes in the PRC2 complex, WNT and AKT signaling pathways, notably all targetable pathways. In an EGFR mutant model transformed by paclitaxel, a significant benefit was shown with osomertanib treatment in combination with the AKT inhibitor, samotolisib, and thus with further evaluation, could possibly be used to slow down or reverse the transformation process. This interview took place during the virtual European Lung Cancer Congress 2022.