2026· Iranian Journal of Basic Medical Sciences· Vol 29, pp. 823 - 843· 0 citations· 123 references
Medicine
TL;DR
The strategies detailed here define a next-generation precision-oncology paradigm capable of anticipating tumor evolution, overcoming resistance, and preventing metastatic relapse, by uniting AI-guided design, circadian reprogramming, dormancy eradication, and logic-gated delivery.
Abstract
Triple-negative breast cancer (TNBC) is defined by profound heterogeneity, dormant metastatic reservoirs, and rapid therapy resistance. Building on our AI-Driven CRISPR Strategies in Breast Cancer framework, CRISPR–Cas9 is emerging as more than a gene-editing tool, capable of restoring circadian integrity, eliminating dormant clones, and re-programming immune surveillance. A structured PubMed, Scopus, and ClinicalTrials.gov review through 2025 integrated mechanistic, preclinical, and early clinical evidence. Beyond standard knockout, base, and prime editing, we highlight chrono-genomic repair of BMAL1/PER2, dormancy-focused synthetic-lethality screens, and genomic-collapse tactics for BRCA1-deficient tumors. Adaptive AI pipelines that iteratively refine guide RNAs and exosome-mimetic carriers, incorporating Boolean logic gates, were also evaluated for self-regulated, tumor-specific delivery. Proof-of-concept studies show that HER2 deletion, TP53 rescue, and ABCB1 silencing enhance chemosensitivity across luminal, HER2-positive, and TNBC models. Circadian restoration expands therapeutic windows and delays relapse in xenografts. Dormancy-directed CRISPR screens reveal unique vulnerabilities in disseminated tumor cells, whereas genomic collapse selectively destroys BRCA1-mutant clones. Integration with CAR-T cells and antibody–drug conjugates amplifies cytotoxicity, and transient nanoparticle or exosome systems improve solid-tumor penetration while minimizing off-target events. CRISPR–Cas9 is transitioning from a molecular scalpel to an adaptive, self-learning therapeutic ecosystem. By uniting AI-guided design, circadian reprogramming, dormancy eradication, and logic-gated delivery, the strategies detailed here define a next-generation precision-oncology paradigm capable of anticipating tumor evolution, overcoming resistance, and preventing metastatic relapse.
The molecular mechanisms of CRISPR-guided knockout, the genetic vulnerabilities it has uncovered in PDAC, the therapeutic strategies emerging from this work, and the delivery systems supporting clinical translation are examined.
Muhammad Shahid Mehmood, Maida Noor, Somal Meraj et al.· Discover Oncology· 0 citations
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology is a cutting-edge genome editing tool based on the adaptive immune mechanism of prokaryotes. This system, which operates through three key stages‒adaptation, expression, and interference‒offers high precision and efficiency in genetic modification. This article explores the mechanisms of CRISPR/Cas action and its applications in hematologic malignancies, breast cancer, colorectal cancer, gastric cancer, and lung cancer. Genome editing has demonstrated significant effectiveness in suppressing tumor growth, enhancing cellular sensitivity to therapy, and developing personalized treatment approaches. CRISPR/Cas enhances the efficacy of Chimeric Antigen Receptor T-cell Therapy (CAR-T) and helps overcome tumor cell resistance to treatment. The technology is also actively utilized in genetic screening to identify gene functions and discover new therapeutic targets. However, several challenges remain, including off-target effects, immune responses, and difficulties in delivering CRISPR components to target cells. This article discusses promising strategies to overcome these limitations, such as the development of novel Cas protein variants, improved delivery methods, and epigenetic approaches. CRISPR/Cas represents one of the most promising tools in molecular biology, providing the ability to precisely investigate gene functions and to develop new experimental strategies for therapeutic intervention. The potential of this technology is defined by its flexibility and applicability across a wide range of tasks‒including target validation, disease modeling, and the generation of advanced cellular products. However, its full integration into clinical practice requires further studies aimed at improving safety, reducing the frequency of unintended effects, and developing reliable delivery systems.
M. Omarov, E. Karacheva, M. M. Arapieva et al.· Сибирский научный медицински...· 0 citations
Key methodological steps for achieving high-efficiency lentiviral transduction and selection are described, enabling the successful application of EPIKOL CRISPR screens in chemoresistant TNBC models.
O. Yedier-Bayram, Elif Ayca Guvener, T. Bagci-Onder· Journal of Visualized Experi...· 0 citations
Patient‐derived organoids (PDOs) have emerged as physiologically relevant cancer models that preserve key genetic, histological, and functional features of the tumors from which they are derived. In parallel, CRISPR‐based perturbation technologies have transformed functional genomics by enabling scalable interrogation of gene function. Their integration provides a powerful framework for identifying cancer dependencies, modeling oncogenic evolution, and investigating mechanisms of drug response and resistance in patient‐relevant settings. This review examines how CRISPR knockout, CRISPR interference/activation, and precision editing approaches have been applied in PDO systems to uncover context‐specific vulnerabilities, reconstruct mutational trajectories, and study tumor heterogeneity. We further compare pooled and arrayed screening formats and discuss what is uniquely enabled by performing CRISPR screens in organoids rather than conventional 2D models. Particular emphasis is placed on the technical and analytical constraints of organoid‐based screening, including variable editing efficiency, clonal bottlenecks, biological heterogeneity, and limited scalability. We argue that the major value of organoid‐based CRISPR screening lies in its ability to identify functionally actionable cancer vulnerabilities in a patient‐contextualized model, while also introducing methodological challenges that must be addressed for robust clinical translation.
J. du Plessis, Aadilah Omar· Cancer Medicine· 0 citations
It is hypothesized that genome-wide CRISPRa screening will uncover subtype-specific genetic dependencies and drug resistance mechanisms, offering novel therapeutic insights in leukemia subtype biology, guiding future personalized treatment strategies.
Jeffrey Sullivan, Xiaozen Wen, Gabriela Flores-Vargas et al.· Journal of Immunology· 0 citations
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, characterized by genetic heterogeneity and the accumulation of mutations in key oncogenes and tumor suppressor genes. CRISPR-Cas9 technology has greatly advanced genetic research by enabling precise genome editing. This review focuses on the innovative applications of CRISPR-Cas9 in CRC research, particularly its role in identifying novel therapeutic targets, elucidating mechanisms of drug resistance, and uncovering metabolic and stem cell pathway alterations in tumorigenesis. We highlight the diverse CRISPR systems, including Cas9, Cas12, Cas13, and advanced variants such as CRISPR activation (CRISPRa), CRISPR interference (CRISPRi), base editing, and prime editing, which have expanded gene knockout studies and enhanced our understanding of CRC. Despite these breakthroughs, challenges such as off-target effects and delivery limitations remain. Ongoing efforts to refine CRISPR technology aim to enhance its precision and clinical applicability, ultimately paving the way for more effective and personalized treatment strategies for CRC. In this review, we explore these advances and focus on the latest developments in CRISPR-based approaches for CRC treatment.
Mohadeseh Hassannia, P. Amirifar· Cancer Treatment and Researc...· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
