Related Experiment Video
Updated: Sep 4, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic
Xiaoyong Ge1,2,3, Zaoqu Liu1,2,3, Siyuan Weng1,2,3
1Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Background:
Pharmacogenomics is crucial for individualized drug therapy and plays an increasingly vital role in precision medicine decision-making. However, pharmacogenomics-based molecular subtypes and their potential clinical significance remain primarily unexplored in lung adenocarcinoma (LUAD).
Methods:
A total of 2065 samples were recruited from eight independent cohorts. Pharmacogenomics data were generated from the profiling of relative inhibition simultaneously in mixtures (PRISM) and the genomics of drug sensitivity in cancer (GDSC) databases. Multiple bioinformatics approaches were performed to identify pharmacogenomics-based subtypes and find subtype-specific properties.
Results:
Three reproducible molecular subtypes were found, which were independent prognostic factors and highly associated with stage, survival status, and accepted molecular subtypes. Pharmacogenomics-based subtypes had distinct molecular characteristics: S-Ⅰ was inflammatory, proliferative, and immune-evasion; S-Ⅱ was proliferative and genetics-driven; S-III was metabolic and methylation-driven. Finally, our study provided subtype-guided personalized treatment strategies: Immune checkpoint blockers (ICBs), doxorubicin, tipifarnib, AZ628, and AZD6244 were for S-Ⅰ; Cisplatin, camptothecin, roscovitine, and A.443654 were for S-Ⅱ; Docetaxel, paclitaxel, vinorelbine, and BIBW2992 were for S-III.
Conclusion:
We provided a novel molecular classification strategy and revealed three pharmacogenomics-based subtypes for LUAD patients, which uncovered potential subtype-related and patient-specific therapeutic strategies.
Insights
This study identifies three pharmacogenomics-based molecular subtypes in lung adenocarcinoma (LUAD). These subtypes offer novel insights into patient stratification and guide personalized treatment strategies for improved outcomes.
Area of Science:
- Oncology
- Pharmacogenomics
- Bioinformatics
Background:
- Pharmacogenomics is key for personalized medicine but its role in lung adenocarcinoma (LUAD) molecular subtypes is underexplored.
- Understanding pharmacogenomics-based subtypes can refine precision medicine approaches in LUAD.
Purpose of the Study:
- To identify and characterize pharmacogenomics-based molecular subtypes in LUAD.
- To explore the clinical significance and therapeutic implications of these subtypes.
Main Methods:
- Analysis of 2065 LUAD samples from eight cohorts using PRISM and GDSC databases.
- Application of bioinformatics approaches to identify pharmacogenomics subtypes and their distinct properties.
Main Results:
- Three reproducible pharmacogenomics-based molecular subtypes (S-I, S-II, S-III) were identified in LUAD.
- These subtypes are independent prognostic factors, associated with stage and survival, and exhibit distinct molecular characteristics (inflammatory, proliferative, immune-evasion, genetics-driven, metabolic, methylation-driven).
- Personalized treatment strategies were proposed for each subtype, including specific drug recommendations like ICBs for S-I, cisplatin for S-II, and taxanes for S-III.
Conclusions:
- A novel molecular classification strategy for LUAD based on pharmacogenomics was developed.
- The identified subtypes provide a basis for patient-specific therapeutic strategies, advancing personalized medicine in LUAD.
