CANCER TYPE–SPECIFIC PATTERNS OF ANTICANCER DRUG SENSITIVITY AND TARGET PATHWAY ASSOCIATIONS IN GDSC2 CELL LINES

Abstract

Anticancer drug response varies substantially across cancer types because of differences in molecular characteristics, therapeutic targets, and pathway dependencies. Large-scale pharmacogenomic resources such as GDSC2 provide an opportunity to examine these variations systematically across diverse cancer cell lines and compounds. This study aimed to compare anticancer drug sensitivity across cancer types and evaluate target pathway–specific response patterns using GDSC2 cell-line data. A secondary-data analysis was conducted using 242,036 drug-response observations from 969 cancer cell lines. Drug sensitivity was assessed using LN_IC50, AUC, and Z-score. Cancer-specific and pathway-specific response patterns were summarized using descriptive statistics, median sensitivity measures, Kruskal–Wallis tests, and Spearman correlation. Drug sensitivity differed significantly across cancer types and target pathways. Hematological malignancies generally showed lower LN_IC50 values than many solid tumors. Mitosis, protein stability and degradation, cell-cycle regulation, and apoptosis were associated with comparatively greater sensitivity. Significant heterogeneity was observed across cancer categories and pathways, while LN_IC50 and AUC showed a strong positive association.  GDSC2 revealed distinct cancer type–specific and pathway-specific patterns of anticancer drug response. These findings support the value of integrated pharmacogenomic screening for identifying therapeutic vulnerabilities and guiding future precision-oncology research.