{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:30:01Z","timestamp":1786595401175,"version":"build-2736575974"},"reference-count":180,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Early cancer detection is critical for improving patient outcomes, yet current diagnostic approaches often fail to identify malignancies when tumor-specific biomarkers are relatively scarce. Emerging CRISPR\/Cas-based technologies have revolutionized the ultra-sensitive detection of cancer biomarkers in liquid biopsies, overcoming the inherent limitations of traditional diagnostic approaches such as tissue biopsies and imaging, which frequently fail to detect early-stage malignancies with sufficient sensitivity. This review explores recent advances in CRISPR\/Cas diagnostics (CRISPR\/Cas-Dx) that employ programmable CRISPR effectors, including Cas9, Cas12, Cas13, and Cas14. In particular, the collateral (trans-) cleavage activities of Cas12, Cas13, and Cas14 enable signal amplification for highly sensitive detection of circulating tumor DNA, microRNAs, exosomes, and other multi-omics biomarkers, often without the need for extensive nucleic acid amplification. Representative CRISPR\/Cas-Dx platforms include amplification-coupled assays, amplification-free frameworks, biosensing and multiplexing capabilities, and new digital or droplet-based configurations that include artificial intelligence to improve analytical precision. These technologies demonstrate single-molecule resolution and adaptability for point-of-care testing in malignancies such as non-small cell lung, colorectal, and breast carcinoma. Finally, we outline a clinical translation roadmap encompassing manufacturability, regulatory and standardization requirements, and real-world implementation challenges. This perspective offers a blueprint for CRISPR-powered, ultra-sensitive liquid biopsy diagnostics that can enable population-scale early cancer screening and truly preventive oncology by bridging molecular insights, engineering innovation, and clinical imperatives.<\/jats:p>","DOI":"10.3390\/diagnostics16162531","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T13:46:16Z","timestamp":1786455976000},"page":"2531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advancements in CRISPR\/Cas Technologies for Sensitive Cancer Detection: Mechanisms, Platforms, and Clinical Translation Roadmap"],"prefix":"10.3390","volume":"16","author":[{"given":"Rokeya","family":"Akter","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8460-7111","authenticated-orcid":false,"given":"Sook Won","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4036-8443","authenticated-orcid":false,"given":"Jong-Han","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea"},{"name":"Research Institute of Metabolism and Inflammation, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaay9040","DOI":"10.1126\/science.aay9040","article-title":"Early detection of cancer","volume":"375","author":"Crosby","year":"2022","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a037333","DOI":"10.1101\/cshperspect.a037333","article-title":"The different facets of liquid biopsy: A kaleidoscopic view","volume":"10","author":"Cayrefourcq","year":"2020","journal-title":"Cold Spring Harb. 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