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Narrowing the focus: a toolkit to systematically connect oncogenic signaling pathways with cancer phenotypes
Katherine R Singleton1, Kris C Wood1
1Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
Abstract:
Functional genomics approaches such as gain- and loss-of-function screening can efficiently reveal genes that control cancer cell growth, survival, signal transduction, and drug resistance, but distilling the results of large-scale screens into actionable therapeutic strategies is challenging given our incomplete understanding of the functions of many genes. Research over several decades, including the results of large-scale cancer sequencing projects, has made it clear that many oncogenic properties are controlled by a common set of core oncogenic signaling pathways. By directly screening this core set of pathways, rather than much larger numbers of individual genes, it may be possible to more directly and efficiently connect functional genomic screening results with therapeutic targets. Here, we describe the recent development of methods to directly screen oncogenic pathways in high-throughput. We summarize the results of studies that have used pathway-centric screening to map the pathways of resistance to targeted therapies in diverse cancer types, then conclude by expanding on potential future applications of this approach.
Insights
Functional genomic screening identifies genes controlling cancer, but pathway-centric screening offers a more direct route to therapeutic targets. This approach efficiently maps resistance pathways to targeted therapies, paving the way for future cancer treatments.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Functional genomics screens identify genes regulating cancer cell growth, survival, signaling, and drug resistance.
- Understanding gene function is crucial for translating screening results into effective cancer therapies.
- Core oncogenic signaling pathways are frequently implicated across various cancer types.
Approach:
- Developed high-throughput methods for direct screening of oncogenic pathways.
- Utilized pathway-centric screening to overcome limitations of individual gene-focused approaches.
- Mapped pathways conferring resistance to targeted therapies in diverse cancers.
Key Points:
- Pathway-centric screening directly connects functional genomics to therapeutic targets.
- Identified key pathways involved in resistance to targeted cancer therapies.
- Demonstrated the efficiency of screening core pathways over individual genes.
Conclusions:
- Pathway-centric screening accelerates the identification of actionable therapeutic strategies.
- This approach holds significant potential for future applications in precision oncology.
- Facilitates a more direct link between large-scale functional genomic data and clinical applications.
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