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Updated: Aug 7, 2025
Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
A CRISPR Path to Finding Vulnerabilities and Solving Drug Resistance: Targeting the Diverse Cancer Landscape and Its
Benjamin McLean1, Aji Istadi1, Teleri Clack2
1The Kinghorn Cancer Centre The Garvan Institute of Medical Research 384 Victoria St, Darlinghurst Sydney New South Wales 2010 Australia.
Abstract:
Cancer is the second leading cause of death globally, with therapeutic resistance being a major cause of treatment failure in the clinic. The dynamic signaling that occurs between tumor cells and the diverse cells of the surrounding tumor microenvironment actively promotes disease progression and therapeutic resistance. Improving the understanding of how tumors evolve following therapy and the molecular mechanisms underpinning de novo or acquired resistance is thus critical for the identification of new targets and for the subsequent development of more effective combination regimens. Simultaneously targeting multiple hallmark capabilities of cancer to circumvent adaptive or evasive resistance may lead to significantly improved treatment response in the clinic. Here, the latest applications of functional genomics tools, such as clustered regularly interspaced short palindromic repeats (CRISPR) editing, to characterize the dynamic cancer resistance mechanisms, from improving the understanding of resistance to classical chemotherapeutics, to deciphering unique mechanisms that regulate tumor responses to new targeted agents and immunotherapies, are discussed. Potential avenues of future research in combating therapeutic resistance, the contribution of tumor-stroma signaling in this setting, and how advanced functional genomics tools can help streamline the identification of key molecular determinants of drug response are explored.
Insights
Understanding cancer
Area of Science:
- Oncology
- Cancer Biology
- Genomics
Background:
- Cancer is a leading global cause of death, with therapeutic resistance significantly hindering treatment success.
- Tumor microenvironment signaling drives cancer progression and resistance.
- Elucidating resistance mechanisms is crucial for developing effective cancer therapies.
Purpose of the Study:
- To review the application of functional genomics tools in understanding cancer therapeutic resistance.
- To explore how these tools can identify new targets and combination strategies.
- To discuss future research directions in combating drug resistance.
Main Methods:
- Review of functional genomics tools, including clustered regularly interspaced short palindromic repeats (CRISPR) editing.
- Analysis of mechanisms underlying resistance to chemotherapeutics, targeted agents, and immunotherapies.
- Exploration of tumor-stroma signaling's role in therapeutic resistance.
Main Results:
- Functional genomics tools, particularly CRISPR, are vital for characterizing dynamic cancer resistance.
- These tools aid in understanding resistance to diverse cancer treatments.
- CRISPR enables deciphering molecular determinants of drug response.
Conclusions:
- Advanced functional genomics tools are essential for overcoming therapeutic resistance.
- Targeting multiple cancer pathways simultaneously may improve treatment outcomes.
- Future research should focus on tumor-stroma interactions and advanced genomics for novel therapeutic strategies.
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