Transcriptomic analysis of therapy-naïve and alectinib-treated H3122 xenograft tumors from NSG and humanized HGF-NSG mice

To uncover the identity of the HGF-independent stromal-mediated resistance mechanism(s), we performed transcriptomic analyses of treatment-naïve and alectinib-treated H3122 xenograft tumors from NSG and humanized HGF-NSG (hHGF-NSG) mice. Xenograft tumors of H3122 cell model were used to perform bulk-RNA sequencing. Reads were mapped to both human and murine genomes, enabling simultaneous assessment of the tumor and stromal compartments. Our transcriptional analyses revealed the emergence of the HGF-dependent differences only after six weeks of alectinib treatment. Pathway enrichment analyses revealed marked changes in multiple pathways associated with extracellular matrix (ECM). Altogether, the transcriptomic analysis supported the potential involvement of tumor cell-ECM interactions in HGF-independent mediation of stromal-mediated resistance to alectinib.