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CRISPR/Cas9 in colorectal cancer: Revolutionizing precision oncology through genome editing and targeted therapeutics
Bahjat Alhasso1, Abdulkareem Shareef2, Lalji Baldaniya3
1College of Pharmacy, Alnoor University, Nineveh, Iraq.
Abstract:
Colorectal cancer (CRC) remains a significant global health challenge, necessitating advanced molecular therapies to improve outcomes. The CRISPR/Cas9 genome-editing platform has emerged as a transformative tool in CRC research, enabling precise genomic modifications to suppress tumor progression, enhance chemosensitivity, and modulate oncogenic pathways. This review highlights CRISPR/Cas9 applications in CRC models, including MC38 murine and CaCO-2 cell lines, where targeted gene edits demonstrate tumor-suppressive effects. For instance, Par3L protein knockout via CRISPR/Cas9 inhibits proliferation, induces apoptosis, and sensitizes cells to chemotherapy by regulating AMPK signaling. Additionally, AAV-mediated CRISPR editing shows promise in HPV16-driven CRC models. Despite its potential, clinical translation faces challenges such as off-target effects, immunogenicity, and delivery limitations. Advances in engineered CRISPR variants (e.g., xCas9, HypaCas9) and innovative delivery systems are refining specificity and efficacy. CRISPR/Cas9 also accelerates biomarker discovery, paving the way for precision oncology. Overcoming current barriers could revolutionize CRC therapeutics, offering personalized treatment paradigms.
Insights
CRISPR/Cas9 gene editing offers new ways to fight colorectal cancer (CRC) by precisely altering genes in cancer cells. This technology shows promise in preclinical models for suppressing tumors and improving treatment responses.
Area of Science:
- Genetics and Genomics
- Oncology
- Molecular Biology
Background:
- Colorectal cancer (CRC) is a major global health concern requiring innovative molecular therapies.
- The CRISPR/Cas9 system provides a powerful platform for precise genome editing in cancer research.
Purpose of the Study:
- To review the applications of CRISPR/Cas9 technology in colorectal cancer research models.
- To highlight the potential of CRISPR/Cas9 in suppressing tumor progression and enhancing therapeutic sensitivity.
- To discuss the challenges and future directions for clinical translation of CRISPR/Cas9 in CRC.
Main Methods:
- Utilized CRISPR/Cas9 in CRC models (MC38, CaCO-2) for targeted gene modifications.
- Investigated the effects of gene knockouts (e.g., Par3L) on cancer cell proliferation, apoptosis, and chemosensitivity.
- Explored adeno-associated virus (AAV)-mediated CRISPR editing in specific CRC models.
Main Results:
- CRISPR/Cas9 gene editing demonstrated tumor-suppressive effects in preclinical CRC models.
- Par3L protein knockout inhibited proliferation, induced apoptosis, and sensitized cells to chemotherapy via AMPK signaling.
- AAV-mediated CRISPR editing showed potential in HPV16-driven CRC models.
Conclusions:
- CRISPR/Cas9 is a transformative tool for CRC research, enabling precise genetic manipulation.
- Overcoming challenges like off-target effects and delivery is crucial for clinical translation.
- CRISPR/Cas9 holds significant promise for advancing precision oncology and personalized CRC therapeutics.
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