A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia.

ABSTRACT: Despite incredible progress in cancer treatment, therapy resistance remains the leading limiting factor for long-term survival. During drug treatment, several genes are transcriptionally upregulated to mediate drug tolerance. Using highly variable genes and pharmacogenomic data for acute myeloid leukemia (AML), we developed a drug sensitivity prediction model for the receptor tyrosine kinase inhibitor sorafenib and achieved more than 80% prediction accuracy. Furthermore, by using Shapley additive explanations for determining leading features, we identified AXL as an important feature for drug resistance. Drug-resistant patient samples displayed enrichment of protein kinase C (PKC) signaling, which was also identified in sorafenib-treated FLT3-ITD-dependent AML cell lines by a peptide-based

SUBMITTER: Nasimian A 

PROVIDER: S-EPMC9959897 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature