Related Experiment Video
Updated: Jun 13, 2025
Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Identifying genetically-supported drug repurposing targets for non-small cell lung cancer through mendelian
Yi Feng1,2, Caichen Li1,2, Bo Cheng1,2
1Dpartment of Thoracic Surgery and Oncology, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Background:
Lung cancer is responsible for most cancer-related deaths, and non-small cell lung cancer (NSCLC) accounts for the majority of cases. Targeted therapy has made promising advancements in systemic treatment for NSCLC over the last two decades, but inadequate drug targets with clinically proven survival benefits limit its universal application in clinical practice compared to chemotherapy and immunotherapy. There is an urgent need to explore new drug targets to expand the beneficiary group. This study aims to identify druggable genes and to predict the efficacy and prognostic value of the corresponding targeted drugs in NSCLC.
Methods:
Two-sample mendelian randomization (MR) of druggable genes was performed to predict the efficacy of their corresponding targeted therapy for NSCLC. Subsequent sensitivity analyses were performed to assess potential confounders. Accessible RNA sequencing data were incorporated for subsequent verifications, and Kaplan-Meier survival curves of different gene expressions were used to explore the prognostic value of candidate druggable genes.
Results:
MR screening encompassing 4,863 expression quantitative trait loci (eQTL) and 1,072 protein quantitative trait loci (pQTL, with 453 proteins overlapping) were performed. Seven candidate druggable genes were identified, including CD33, ENG, ICOSLG and IL18R1 for lung adenocarcinoma, and VSIR, FSTL1 and TIMP2 for lung squamous cell carcinoma. The results were validated by further transcriptomic investigations.
Conclusions:
Drugs targeting genetically supported genomes are considerably more likely to yield promising efficacy and succeed in clinical trials. We provide compelling genetic evidence to prioritize drug development for NSCLC.
Insights
This study identifies seven druggable genes for non-small cell lung cancer (NSCLC) using Mendelian randomization. These genetic targets show promise for developing new NSCLC therapies with improved efficacy.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) causes significant cancer mortality.
- Targeted therapies offer advancements but face limitations due to insufficient drug targets.
- New therapeutic targets are crucial for expanding NSCLC treatment options.
Purpose of the Study:
- To identify druggable genes in NSCLC.
- To predict the efficacy of targeted drugs for NSCLC.
- To evaluate the prognostic value of candidate genes in NSCLC.
Main Methods:
- Two-sample Mendelian randomization (MR) was employed to assess gene-drug target associations.
- Sensitivity analyses were conducted to address potential confounders.
- RNA sequencing data and Kaplan-Meier curves were used for validation and prognostic assessment.
Main Results:
- MR screening identified seven candidate druggable genes.
- Specific genes (CD33, ENG, ICOSLG, IL18R1) were linked to lung adenocarcinoma.
- Other genes (VSIR, FSTL1, TIMP2) were associated with lung squamous cell carcinoma.
- Transcriptomic data validated these findings.
Conclusions:
- Genetically supported drug targets are more likely to succeed in clinical trials.
- This study provides genetic evidence to guide NSCLC drug development.
- Prioritizing these identified genes can accelerate the development of effective NSCLC therapies.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...