{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:01:20Z","timestamp":1785427280819,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Basic and Applied Basic Research Foundation of Guangdong Province","award":["2025A1515012742 and 2023A1515010417"],"award-info":[{"award-number":["2025A1515012742 and 2023A1515010417"]}]},{"name":"the Beijing Xisike Clinical Oncology Research Foundation","award":["Y-Gilead2024-PT-0006"],"award-info":[{"award-number":["Y-Gilead2024-PT-0006"]}]},{"award":["Y-Gilead2024-PT-0006"],"award-info":[{"award-number":["Y-Gilead2024-PT-0006"]}],"id":[{"id":"https:\/\/ror.org\/05sfnze82","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Sacituzumab govitecan (SG, IMMU-132) is a TROP2-directed antibody\u2013drug conjugate carrying SN-38. Patients with colorectal liver metastasis (CRLM) still have limited treatment options after first-line systemic therapy, and the preclinical pharmacological value of TROP2-directed SN-38 delivery in CRLM remains insufficiently defined. Methods: Public single-cell RNA-sequencing data were reanalyzed to explore the distribution of TACSTD2\/TROP2-positive epithelial-associated cells in adjacent normal tissues, primary colorectal cancer, and CRLM. The prognostic relevance of TACSTD2 was evaluated using the Kaplan\u2013Meier Plotter database. TROP2-knockdown and TROP2-overexpressing colorectal cancer models were used to assess IMMU-132 response in vitro and in vivo. Pharmacological antitumor activity was further evaluated using subcutaneous xenografts, syngeneic intrasplenic liver metastasis models, and CRLM patient-derived organoids (PDOs). Transcriptomic profiling and \u03b3-H2AX immunofluorescence were used to explore treatment-associated molecular changes. Results: At the patient\/sample level, TACSTD2\/TROP2-positive epithelial-associated cells showed numerically higher proportions in primary colorectal tumors and liver metastases than in adjacent normal tissues, and high TACSTD2 expression was associated with inferior overall survival in a public survival database. TROP2 knockdown attenuated IMMU-132-induced growth inhibition, apoptosis, and suppression of colony formation. In vivo, IMMU-132 suppressed colorectal tumor growth and reduced liver metastatic burden, with more evident activity in human TROP2-overexpressing models. In a limited exploratory CRLM PDO cohort established after first-line therapy, liver metastasis-derived PDOs showed lower normalized AUC values than primary tumor-derived PDOs. Transcriptomic analysis and representative \u03b3-H2AX immunofluorescence suggested that IMMU-132 treatment was associated with changes in adhesion\/cytoskeletal-related pathways, Wnt\/cancer-associated transcriptional programs, and DNA damage-associated signals. Conclusions: These in vitro, in vivo, and PDO-based findings support further preclinical pharmacological evaluation of TROP2-directed SN-38 delivery by IMMU-132 in biomarker-annotated CRLM models, particularly in the post-first-line systemic therapy setting.<\/jats:p>","DOI":"10.3390\/ph19081163","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:26:23Z","timestamp":1785115583000},"page":"1163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Pharmacological Evaluation of Sacituzumab Govitecan (IMMU-132) in TROP2-Positive Colorectal Liver Metastasis Models"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4703-3486","authenticated-orcid":false,"given":"Weili","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruowei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingting","family":"Situ","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0769-8195","authenticated-orcid":false,"given":"Jianhong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhai","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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