{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:10:14Z","timestamp":1785431414196,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82373354"],"award-info":[{"award-number":["82373354"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82373354"],"award-info":[{"award-number":["82373354"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LTGY23H160025"],"award-info":[{"award-number":["LTGY23H160025"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["JHSZ26H160001"],"award-info":[{"award-number":["JHSZ26H160001"]}]},{"award":["LTGY23H160025"],"award-info":[{"award-number":["LTGY23H160025"]}],"id":[{"id":"https:\/\/ror.org\/04aqat463","id-type":"ROR","asserted-by":"publisher"}]},{"award":["JHSZ26H160001"],"award-info":[{"award-number":["JHSZ26H160001"]}],"id":[{"id":"https:\/\/ror.org\/04aqat463","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Major Projects of Jinhua Science and Technology Research Program","award":["2025-03-004"],"award-info":[{"award-number":["2025-03-004"]}]},{"name":"Key Projects of Jinhua Science and Technology Research Program","award":["2026-3-039"],"award-info":[{"award-number":["2026-3-039"]}]},{"name":"Key Projects of Jinhua Science and Technology Research Program","award":["2023-3-111"],"award-info":[{"award-number":["2023-3-111"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chemotherapy resistance remains a major challenge in colorectal cancer (CRC) treatment, necessitating novel adjuvant strategies. This study employed an integrated analytical strategy combining network pharmacology, single-cell RNA sequencing (scRNA-seq) of patient-derived organoids (PDOs) and molecular dynamics simulations to identify bioactive compounds from Ganoderma lucidum and elucidate their chemo-sensitizing mechanisms. Network pharmacology identified five bioactive components of G. lucidum, corresponding to 267 potential targets. Integration with transcriptomic data, weighted gene co-expression network analysis (WGCNA), and known CRC genes refined these to 19 core targets. Cross-referencing with scRNA-seq data from irinotecan-treated PDOs pinpointed cyclin-dependent kinase 2 (CDK2) and Aurora kinase A (AURKA) as pivotal targets. Molecular dynamics simulations confirmed stable binding of the key component cerevisterol to both CDK2 and AURKA proteins, with binding free energies of \u2212120.67 kJ\/mol and \u2212134.47 kJ\/mol, respectively. In vitro cell viability assays across multiple CRC cell lines (HCT116, RKO, and HT-29) and PDOs demonstrated that cerevisterol significantly sensitized CRC cells to irinotecan (SN38). Notably, we observed that CDK2 was preferentially enriched in MSI-H tumors, whereas AURKA was enriched in MSS tumors, suggesting the potential of MSI status as a biomarker for patient stratification. Collectively, these findings identify cerevisterol as a dual-targeting natural product that modulates CDK2 and AURKA to overcome chemotherapy resistance, providing a quantitative analytical framework for discovering bioactive compounds and their molecular targets from medicinal fungi.<\/jats:p>","DOI":"10.3390\/ijms27146120","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:27:31Z","timestamp":1783531651000},"page":"6120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting CDK2 and AURKA with Cerevisterol from Ganoderma lucidum to Sensitize Colorectal Cancer to Chemotherapy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0725-5685","authenticated-orcid":false,"given":"Yi","family":"Pan","sequence":"first","affiliation":[{"name":"Central Laboratory, Precision Medicine Center, Affiliated Jinhua Hospital, Zhejiang University School 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