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Updated: Aug 22, 2026

Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
Published on: October 3, 2025
Predicting drug response based on gene expression
Jacques Robert1, Antoine Vekris, Philippe Pourquier
1Institut Bergonié and Université Victor Segalen Bordeaux 2, 229 cours de l'Argonne, 33076 Bordeaux, France. robert@bergionie.org
Abstract:
Predicting drug response is a challenging problem in oncology. In the 1975-1985 decade, important efforts were devoted to the generation of cellular assays able to predict, on an individual basis, the in vitro response of tumour cells to chemotherapeutic agents, but such methods could not be adopted in routine. Numerous mechanisms of resistance to anticancer agents have been identified in cultured cell lines selected for growth in the presence of infratoxic, increasing doses of anticancer agents. They mainly concern drug transport, drug activation or detoxification, target quantitative or qualitative alterations, DNA repair efficiency, and alterations in signalling and/or execution of cell death programmes. New molecular biology techniques have been developed in order to identify the genes involved in drug resistance; they mainly involve differential expression techniques, but functional approaches may also prove informative. The availability of techniques of gene expression profiling has allowed to establish correlations between gene expression and drug sensitivity of tumour cells or human cancers. This type of approach has been initiated on in vitro systems by the National Cancer Institute (NCI) in the USA and is pursued by a growing number of public and private laboratories around the world. In the clinical setting, a number of genes or proteins have been identified as potential predictive markers of drug activity and their use could be progressively implemented for drug selection in patients receiving chemotherapy, allowing thus more rational and individualised treatments.
Insights
Predicting cancer drug response remains difficult. Research identifies drug resistance mechanisms and uses gene expression profiling to correlate gene activity with drug sensitivity, aiming for personalized cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacogenomics
Background:
- Predicting individual patient response to chemotherapy is a significant challenge in cancer treatment.
- Historically, cellular assays for predicting in vitro drug response faced limitations in routine clinical adoption.
- Numerous mechanisms of anticancer drug resistance have been identified in cell lines, including issues with drug transport, metabolism, target alteration, DNA repair, and cell death pathways.
Purpose of the Study:
- To review the mechanisms of anticancer drug resistance.
- To explore the role of molecular biology techniques, particularly gene expression profiling, in understanding drug sensitivity.
- To discuss the potential of identified genes and proteins as predictive markers for personalized chemotherapy selection.
Main Methods:
- Identification of drug resistance mechanisms in cultured cancer cell lines.
- Application of molecular biology techniques, including differential gene expression analysis.
- Utilizing gene expression profiling to correlate gene activity with drug sensitivity in vitro and in human cancers.
Main Results:
- Established correlations between gene expression patterns and the drug sensitivity of tumor cells.
- Identified specific genes and proteins implicated in various drug resistance mechanisms.
- Demonstrated the feasibility of using gene expression data to predict drug response.
Conclusions:
- Gene expression profiling offers a powerful approach to understand and predict anticancer drug response.
- Identifying predictive markers holds promise for developing more rational and individualized cancer chemotherapy strategies.
- The integration of molecular data into clinical practice could significantly improve patient outcomes.
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