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Whole-genome mapping of small-molecule targets for cancer medicine
Stéphanie Solier1, Sebastian Müller1, Raphaël Rodriguez1
1Institut Curie, 26 rue d'Ulm, 75248, Paris, Cedex 05, France; PSL Université Paris, France; Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, France.
Abstract:
Cancers display intratumoral and intertumoral heterogeneity, which poses challenges to small-molecule intervention. Studying drug responses on a whole-genome and transcriptome level using next-generation sequencing has revolutionized our understanding of how small molecules intervene in cells, which helps us to study and potentially predict treatment outcomes. Some small molecules act directly at the genomic level by targeting DNA or chromatin proteins. Here, we review recent advances in establishing whole-genome and transcriptome maps of small-molecule targets, comprising chromatin components or downstream events. We also describe recent advances in studying drug responses using single-cell RNA and DNA sequencing. Furthermore, we discuss how this fundamental research can be taken forward to devise innovative personalized treatment modalities.
Insights
Cancer heterogeneity complicates drug treatment. Next-generation sequencing advances reveal how small molecules target cancer genomes and transcriptomes, aiding personalized medicine development.
Area of Science:
- Genomics and Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Intratumoral and intertumoral heterogeneity in cancers presents significant challenges for effective small-molecule intervention.
- Next-generation sequencing (NGS) technologies have transformed the study of drug responses at the whole-genome and transcriptome levels.
- Understanding how small molecules interact with cellular components is crucial for predicting treatment outcomes.
Purpose of the Study:
- To review recent advancements in mapping small-molecule targets at the whole-genome and transcriptome levels.
- To highlight progress in utilizing single-cell RNA and DNA sequencing for studying drug responses.
- To discuss the potential of this research in developing innovative personalized cancer treatment strategies.
Main Methods:
- Review of recent scientific literature on small-molecule target identification and drug response studies.
- Focus on whole-genome and transcriptome mapping techniques.
- Integration of single-cell sequencing data (RNA and DNA) for detailed analysis.
Main Results:
- Establishment of comprehensive genomic and transcriptomic maps for small-molecule targets, including chromatin proteins and downstream effectors.
- Demonstration of single-cell sequencing's utility in dissecting heterogeneous cellular responses to drugs.
- Identification of key areas for future research in personalized oncology.
Conclusions:
- Advances in genomic and transcriptomic analysis, particularly single-cell sequencing, offer powerful tools to understand and overcome cancer heterogeneity.
- This fundamental research provides a foundation for developing novel, personalized therapeutic strategies targeting specific molecular profiles in cancer patients.
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