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World J Gastrointest Oncol. Apr 15, 2026; 18(4): 114220
Published online Apr 15, 2026. doi: 10.4251/wjgo.v18.i4.114220
Published online Apr 15, 2026. doi: 10.4251/wjgo.v18.i4.114220
HMGCR loss is synthetic lethal with PIK3CD inhibition in colorectal cancer cells
Jin-Hui Huang, Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
Jin-Qi Ma, Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
Author contributions: Huang JH was responsible for methodology, formal analysis, data curation, software, investigation, writing—original draft, visualization; Ma JQ was responsible for acquisition, project administration, conceptualization, resources, supervision, writing—review & editing; both authors contributed to study conception and design, and have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the IRB of the Third Xiangya Hospital of Central South University (Approval No. 2018-S124).
Institutional animal care and use committee statement: The laboratory animals were approved by the Medical Laboratory Animal Ethics Committee of the Third Xiangya Hospital of Central South University (Approval No. XMSB-2024-0037).
Conflict-of-interest statement: The authors declare no conflicts of interest in this study.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data that support the findings of our study are available from the corresponding author Jin-Qi Ma (601237@csu.edu.cn).
Corresponding author: Jin-Qi Ma, MD, Professor, Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha 410013, Hunan Province, China. 601237@csu.edu.cn
Received: September 16, 2025
Revised: November 23, 2025
Accepted: January 26, 2026
Published online: April 15, 2026
Processing time: 206 Days and 16.2 Hours
Revised: November 23, 2025
Accepted: January 26, 2026
Published online: April 15, 2026
Processing time: 206 Days and 16.2 Hours
Core Tip
Core Tip: Integrated analysis of data from the SOLAD, CSSL, and SynLethDB databases was performed to identify HMGCR as a PIK3CD-interacting synthetic lethal partner. Atorvastatin in combination with gefitinib synergistically inhibited the proliferation and metastasis of colorectal cancer (CRC) cells through a synthetic lethal effect via the AMP-activated protein kinase-sterol regulatory element-binding protein 1 signaling pathway. This study provides new research ideas for CRC treatment.