ArticleSignal transduction and targeted therapy2025
An aptamer-drug conjugate for promising cancer therapy with comprehensive evaluation from rodents to non-human primates.
Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Research progress of aptamers in the diagnosis and treatment of colorectal cancer (Review).Molecular medicine reports · 2026Review
- Fast tumor accumulation and payload release of c-Met targeting aptamer-drug conjugate enables robust anti-tumor efficacy.Cell reports. Medicine · 2026Article
- Nucleic acid aptamers: new methods for selection, target validation, molecular diagnostics and therapeutics.Signal transduction and targeted therapy · 2026Review
- Antibody-Drug Conjugates and Peptide-Drug Conjugates: Current Understandings and Future Perspectives.MedComm · 2026Review
- Engineered CRISPR/Cas12a2 Nanoprobe Imaging in Living Cells for Precise Tumor Diagnosis.Small methods · 2026Article
- Pharmacological perturbation of splicing elicits SMG1 reduction: Implications for cancer therapy.iScience · 2026Article
- Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026Review
- Aptamers and aptamer-drug conjugates as synthetic immune modulators for cancer immunotherapy.Frontiers in immunology · 2026Review
- Dual-Mechanism Aptamer-Drug Complex Overcomes Paclitaxel Resistance in Ovarian Cancer via Structural Constraint and Telomerase Inhibition.Research (Washington, D.C.) · 2026Article
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Authors and funding
19 authors.
Funding
Abstract
Aptamers serve as unique targeting ligands, making aptamer-drug conjugates (ApDCs) an attractive strategy for targeted cancer therapy. This study performs a comprehensive evaluation from rodents to non-human primates (NHP) of a protein tyrosine kinase 7 (PTK7)-targeted ApDC (Sgc8c-M) made by conjugating the potent antimitotic agent monomethyl auristatin E (MMAE) to the classic PTK7 aptamer Sgc8c. Efficacy studies in various cancer types with PTK7 overexpression showed that Sgc8c-M effectively induces sustained tumor regression in cell line-derived and patient-derived xenografts, outperforming unconjugated MMAE, the chemotherapy drug paclitaxel, and a PTK7-targeted antibody-drug conjugate. Pharmacokinetic (PK) studies in mice revealed that Sgc8c-M leads to rapid accumulation and sustained MMAE levels in tumors, along with fast clearance from plasma and normal tissues. Further study in rats confirmed rapid clearance across most organs and revealed that over 75% of MMAE was excreted through urine and feces within 24 h. Toxicokinetic (TK) assessments indicated comparable systemic drug exposure without accumulation for repeated doses compared to single administration. Toxicity evaluations showed that the therapeutic dose with high efficacy was safe and that the toxicity resulting from extremely high doses could be reversibly controlled. Encouraged by these findings, we evaluated PK/TK profiles and safety of Sgc8c-M in cynomolgus monkeys. Similar to PK/TK profiles observed in rats, Sgc8c-M demonstrated good dose-dependent drug exposure. It was, moreover, well tolerated in monkeys with no obvious accumulation following multiple administrations. These findings highlight the potential of Sgc8c-M as an effective antitumor agent and provide useful insights for the clinical translation of emerging ApDCs.
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