ArticleCancer science2021
Quadruple-editing of the MAPK and PI3K pathways effectively blocks the progression of KRAS-mutated colorectal cancer cells.
Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Cancer Stem Cells in Colorectal Cancer: From Molecular Mechanisms to Diagnosis, Prognosis and Therapy Implications.Cancers · 2026Review
- A review on applications and safety of 222 nm far UVC light for surface and air disinfection.Biophysical reviews · 2026Review
- Atlas-Guided Nanocarrier Strategies Targeting Spatial NTRK2/MAPK Signaling in EGFR-TKI-Resistant Niches of Esophageal Squamous Cell Carcinoma.Pharmaceutics · 2026Review
- Rapid establishment of KRAS-driven bladder cancer initiation and immune escape models using genetically engineered mice and organoid approaches.Frontiers in immunology · 2026Article
- Aquaporin 9 downregulation in KRASScientific reports · 2025Article
- Selective PI3Kδ inhibitor TYM-3-98 suppresses AKT/mTOR/SREBP1-mediated lipogenesis and promotes ferroptosis in KRAS-mutant colorectal cancer.Cell death & disease · 2024Article
- Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy.Molecular cancer · 2024Review
- Application of CRISPR-Cas9 gene editing technology in basic research, diagnosis and treatment of colon cancer.Frontiers in endocrinology · 2023Review
- Quadruple-editing of the MAPK and PI3K pathways effectively blocks the progression of KRAS-mutated colorectal cancer cells.Cancer science · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutated KRAS promotes the activation of the MAPK pathway and the progression of colorectal cancer (CRC) cells. Aberrant activation of the PI3K pathway strongly attenuates the efficacy of MAPK suppression in KRAS-mutated CRC. The development of a novel strategy targeting a dual pathway is therefore highly essential for the therapy of KRAS-mutated CRC. In this study, a quadruple-depleting system for the KRAS, MEK1, PIK3CA, and MTOR genes based on CRISPR/SaCas9 was developed. Adenovirus serotype 5 (ADV5) was integrated with two engineered proteins, an adaptor and a protector, to form ADV-protein complex (APC) for systemic delivery of the CRISPR system. Quadruple-editing could significantly inhibit the MAPK and PI3K pathways in CRC cells with oncogenic mutations of KRAS and PIK3CA or with KRAS mutation and compensated PI3K activation. Compared with MEK and PI3K/MTOR inhibitors, quadruple-editing induced more significant survival inhibition on primary CRC cells with oncogenic mutations of KRAS and PIK3CA. The adaptor specifically targeting EpCAM and the hexon-shielding protector could dramatically enhance ADV5 infection efficiency to CRC cells and significantly reduce off-targeting tropisms to many organs except the colon. Moreover, quadruple-editing intravenously delivered by APC significantly blocked the dual pathway and tumor growth of KRAS-mutated CRC cells, without influencing normal tissues in cell- and patient-derived xenograft models. Therefore, APC-delivered quadruple-editing of the MAPK and PI3K pathways shows a promising therapeutic potential for KRAS-mutated CRC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.