In vivo functional screening for systems-level integrative cancer genomics
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Updated: Dec 15, 2025
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Published on: November 2, 2020
Julia Weber1,2, Christian J Braun1,3,4, Dieter Saur2,5,6,7
1Institute of Molecular Oncology and Functional Genomics, TUM School of Medicine, Technische Universität München, Munich, Germany.
Abstract:
With the genetic portraits of all major human malignancies now available, we next face the challenge of characterizing the function of mutated genes, their downstream targets, interactions and molecular networks. Moreover, poorly understood at the functional level are also non-mutated but dysregulated genomes, epigenomes or transcriptomes. Breakthroughs in manipulative mouse genetics offer new opportunities to probe the interplay of molecules, cells and systemic signals underlying disease pathogenesis in higher organisms. Herein, we review functional screening strategies in mice using genetic perturbation and chemical mutagenesis. We outline the spectrum of genetic tools that exist, such as transposons, CRISPR and RNAi and describe discoveries emerging from their use. Genome-wide or targeted screens are being used to uncover genomic and regulatory landscapes in oncogenesis, metastasis or drug resistance. Versatile screening systems support experimentation in diverse genetic and spatio-temporal settings to integrate molecular, cellular or environmental context-dependencies. We also review the combination of in vivo screening and barcoding strategies to study genetic interactions and quantitative cancer dynamics during tumour evolution. These scalable functional genomics approaches are transforming our ability to interrogate complex biological systems.
Insights
Functional genomics screens in mice, using tools like CRISPR, are crucial for understanding cancer. These methods help unravel gene functions, molecular networks, and drug resistance in complex biological systems.
Area of Science:
- Genomics
- Cancer Biology
- Functional Genomics
Background:
- The genetic basis of human cancers is increasingly understood, but functional characterization of mutated and dysregulated genes remains a challenge.
- Understanding the interplay of molecular, cellular, and systemic factors in disease pathogenesis requires advanced experimental models.
- Manipulative mouse genetics provides powerful tools to investigate complex biological systems in vivo.
Purpose of the Study:
- To review functional screening strategies in mice for understanding cancer biology.
- To outline genetic tools and their applications in uncovering cancer-related genomic and regulatory landscapes.
- To highlight the integration of in vivo screening with barcoding for studying genetic interactions and cancer evolution.
Main Methods:
- Genetic perturbation and chemical mutagenesis in mice.
- Utilizing genetic tools such as transposons, CRISPR, and RNA interference (RNAi).
- Employing genome-wide or targeted screening approaches, including in vivo screening with barcoding strategies.
Main Results:
- Functional screens are uncovering the roles of mutated genes and identifying targets, interactions, and networks in oncogenesis, metastasis, and drug resistance.
- These approaches reveal genomic and regulatory landscapes crucial for cancer development.
- In vivo screening combined with barcoding enables the study of genetic interactions and quantitative cancer dynamics during tumor evolution.
Conclusions:
- Scalable functional genomics approaches in mice are transforming the interrogation of complex biological systems in cancer research.
- These methods are essential for deciphering the functional consequences of genetic alterations and dysregulations in malignancy.
- The application of diverse genetic tools and screening systems provides integrated insights into molecular, cellular, and environmental context-dependencies in disease.
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