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[Towards Development of Innovative Cancer Therapies - Trans-OMICS Approach]
Reika Kawabata-Iwakawa1, Masahiko Nishiyama
1Dept. of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine.
Abstract:
Comprehensive genomic and transcriptome analyses using next-generation sequencing(NGS)analysis has lead a discovery of a variety of novel driver gene mutations and new therapeutic targets for cancer patients, and has remarkably improved outcome of the patients through the development novel molecular targeting drugs. Even so, in so-called intractable or refractory cancers, those "druggable"alterations common to the diseases are rarely found due to the high diversity of the tumor. Furthermore, most of molecular target therapy is known to acquire the resistance to the drug by means of multiple factors such as up-regulation of the partially inhibited pathway, mutation of the target, activation of alternative pathways, histological translocation, and oncogene de-addiction. Understanding of intra-tumoral heterogeneity and tumor-stromal crosstalk in tumor microenvironment with consequence of biological network re-construction are also of key importance to overcome the resistance. These suggest the limitation of mono-layer OMIC approach focusing on genome and/or cancer cell alone to identify truly effective therapeutic target and biomarker. Under these circumstances,"Trans-OMICS" concept has emerged as a novel approach to clarify a global biochemical network across multiple omics layers(eg genome, transcriptome, proteome, and metabolome)directly correct with a variable phenotype by use of both multi-omic measurements and computational data integration. This approach has great potential for drug discovery and clinical implementation of omics-based cancer medicine. We introduce here the outline of technologies and analysis for Trans-OMICS approach, and review for the recent studies in oncology research with showing our recent attempt.
Insights
Next-generation sequencing (NGS) advanced cancer therapy, but resistance persists in difficult cancers. Trans-OMICS offers a new approach by integrating multiple data types to discover novel targets and biomarkers for improved cancer medicine.
Area of Science:
- Oncology
- Genomics
- Systems Biology
Background:
- Next-generation sequencing (NGS) has identified novel cancer driver mutations and therapeutic targets, improving patient outcomes.
- Intractable or refractory cancers often lack common druggable alterations due to high tumor diversity.
- Acquired resistance to molecular targeted therapy arises from various factors, including pathway alterations and tumor microenvironment interactions.
Purpose of the Study:
- To address the limitations of single-omic approaches in identifying effective cancer therapeutic targets and biomarkers.
- To introduce the Trans-OMICS concept for a comprehensive understanding of cancer biology.
- To highlight the potential of Trans-OMICS in drug discovery and clinical applications for cancer medicine.
Main Methods:
- Utilizing multi-omic measurements (genome, transcriptome, proteome, metabolome) to capture a global biochemical network.
- Employing computational data integration to connect multi-omic data with variable phenotypes.
- Reviewing recent oncology research employing the Trans-OMICS approach.
Main Results:
- Trans-OMICS enables clarification of global biochemical networks across multiple omics layers.
- This approach directly correlates multi-omic data with observable phenotypes.
- The study reviews recent applications and presents the authors' own attempts in oncology research.
Conclusions:
- The Trans-OMICS approach overcomes limitations of single-omic studies for identifying cancer targets.
- Integrating multiple omics layers provides a more holistic view of cancer biology and resistance mechanisms.
- Trans-OMICS holds significant potential for advancing drug discovery and personalized cancer medicine.
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