ArticleMolecular cancer therapeutics2024
Raludotatug Deruxtecan, a CDH6-Targeting Antibody-Drug Conjugate with a DNA Topoisomerase I Inhibitor DXd, Is Efficacious in Human Ovarian and Kidney Cancer Models.
Article in Molecular cancer therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 24 citations in OpenAlex.
- Preclinical evaluation of SLC35D3-targeted CAR-T cells for tumor-selective immunotherapy.Biochemistry and biophysics reports · 2026Article
- Antibody-drug conjugates in gynaecological cancers: opportunities and challenges.Nature reviews. Clinical oncology · 2026Review
- Circulating tumour cells for guiding antibody‒drug conjugate therapy: Role of artificial intelligence.Clinical and translational medicine · 2026Review
- Review
- Pathophysiological and Molecular Features of DXd ADC-Related Interstitial Pneumonitis in Cynomolgus Monkeys.Cancer science · 2026Article
- Treatment Advances in Gynecologic Cancers: Insights From Recent Clinical Trials.Cancer innovation · 2026Review
- Cyclin E1 overexpression identifies a therapeutically relevant poor prognostic patient subgroup in high-grade serous ovarian cancer.NPJ precision oncology · 2026Article
- Homologous recombination deficiency tumor tissue testing in a real-world cohort of tubo-ovarian carcinoma patients: validation of decentralized genomic profiling in 4777 cases.Virchows Archiv : an international journal of pathology · 2026Article
- An antibody-drug conjugate designed through clone and isotype selection restricts the growth of CSPG4-expressing triple-negative breast cancer.NPJ precision oncology · 2026Article
- Formulation Matters: The Overlooked Engine of Stability and Success in Antibody-Drug Conjugates.Pharmaceuticals (Basel, Switzerland) · 2026Review
- HER3 upregulation reduces DS-8201 sensitivity in HER2-positive tumor cells by ATR/CHK1/FoxO1 signaling cascade.Acta pharmacologica Sinica · 2026Article
- Development and application of antibody-drug conjugates in gynecological cancers.Science China. Life sciences · 2026Review
- DS-3939a: A TA-MUC1-Directed Antibody-Drug Conjugate with Broad Antitumor Activity.Molecular cancer therapeutics · 2026Article
- Biomarker-Driven Treatments for Ovarian Cancer: Moving Beyond HRD?International journal of women's health · 2026Review
- Molecular profile and targeted therapies for ovarian clear cell ovarian cancer.Therapeutic advances in medical oncology · 2026Review
- Advances in Phase III Clinical Trials and Future Challenges of Targeted Therapy in Advanced Ovarian Cancer.Cancer management and research · 2026Review
- The Search for Predictive Biomarkers in Response to Immune Checkpoint Inhibitors and Associated Adverse Events.Journal of personalized medicine · 2025Review
- Reticulocalbin-1 in clear cell renal cell carcinoma: clinical and functional evidence for its role as a biomarker and potential therapeutic target.BMC cancer · 2025Article
- CUSP06, a Novel CDH6-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Efficacy in Multiple CDH6-Expressing Human Cancer Models.Pharmaceutics · 2025Article
- Therapeutic landscape of ovarian cancer: recent advances and emerging therapies.Biomarker research · 2025Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 2 countries.
Funding
Abstract
Cadherin-6 (CDH6) is expressed in several cancer types, but no CDH6-targeted therapy is currently clinically available. Here, we generated raludotatug deruxtecan (R-DXd; DS-6000), a novel CDH6-targeting antibody-drug conjugate with a potent DNA topoisomerase I inhibitor, and evaluated its properties, pharmacologic activities, and safety profile. In vitro pharmacologic activities and the mechanisms of action of R-DXd were assessed in serous-type ovarian cancer and renal cell carcinoma cell lines. In vivo pharmacologic activities were evaluated with several human cancer cell lines and patient-derived xenograft mouse models. The safety profile in cynomolgus monkeys was also assessed. R-DXd exhibited CDH6 expression-dependent cell growth-inhibitory activity and induced tumor regression in xenograft models. In this process, R-DXd specifically bound to CDH6, was internalized into cancer cells, and then translocated to the lysosome. The DXd released from R-DXd induced the phosphorylation of Chk1, a DNA damage marker, and cleaved caspase-3, an apoptosis marker, in cancer cells. It was also confirmed that the DXd payload had a bystander effect, passing through the cell membrane and impacting surrounding cells. The safety profile of R-DXd was favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys. R-DXd demonstrated potent antitumor activity against CDH6-expressing tumors in mice and an acceptable safety profile in monkeys. These findings indicate the potential of R-DXd as a new treatment option for patients with CDH6-expressing serous-type ovarian cancer and renal cell carcinoma in a clinical setting.
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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.