biostudies-literatureUnknown13(1)Daum AK<h4>Background</h4>Targeted therapy interventions using tyrosine kinase inhibitors (TKIs) provide encouraging treatment responses in patients with ALK-rearranged lung adenocarcinomas, yet resistance occurs almost inevitably. In addition to tumor cell-intrinsic resistance mechanisms, accumulating evidence suggests that cancer-associated fibroblasts (CAFs) within the tumor microenvironment contribute to therapy resistance. This study aimed to investigate CAF-driven molecular networks that shape the therapeutic susceptibility of ALK-driven lung adenocarcinoma cells.<h4>Methods</h4>Three-dimensional (3D) spheroid co-cultures comprising ALK-rearranged lung adenocarcinoma cells and CAFs were utilized to model the tumor microenvironment. Single-cell RNA sequencing was performed to uncover transcrCancer & metabolism28https://www.ebi.ac.uk/biostudies/studies/S-EPMC12168422biostudies-literatureCancer-associated fibroblasts promote drug resistance in ALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis.PMC12168422Thomas MMuley TKlingmuller USultmann HDaum AKSchulze ASchneider MASchlicker LChristopoulos PfalseCancer-associated fibroblasts promote drug resistance in ALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis.<h4>Background</h4>Targeted therapy interventions using tyrosine kinase inhibitors (TKIs) provide encouraging treatment responses in patients with ALK-rearranged lung adenocarcinomas, yet resistance occurs almost inevitably. In addition to tumor cell-intrinsic resistance mechanisms, accumulating evidence suggests that cancer-associated fibroblasts (CAFs) within the tumor microenvironment contribute to therapy resistance. This study aimed to investigate CAF-driven molecular networks that shape the therapeutic susceptibility of ALK-driven lung adenocarcinoma cells.<h4>Methods</h4>Three-dimensional (3D) spheroid co-cultures comprising ALK-rearranged lung adenocarcinoma cells and CAFs were utilized to model the tumor microenvironment. Single-cell RNA sequencing was performed to uncover transcr2025-01-01T00:00:00Z2025 Jun2026-06-02T22:38:15.722Z2026-04-21T03:13:47.899ZS-EPMC121684224052425310.1186/s40170-025-00400-7