Takashi Nakada
Daiichi Sankyo
CancerTopoisomeraseChemistryApoptosisConjugateTherapeutic indexIn vitroIn vivoGiSTRegorafenibStromal tumorAntibody-drug conjugateImatinibSacituzumab govitecanSunitinibCamptothecinGrowth inhibitionTrastuzumabDrug deliveryExatecanTopoisomerase-I InhibitorDNA Topoisomerase IPDGFRATyrosine kinaseCancer researchClinical trialMonoclonal antibodyCell growthMedicineBiologyPharmacology
14Publications
5H-index
313Citations
Publications 16
Newest
#1Daisuke Okajima (Daiichi Sankyo)H-Index: 4
#2Satoru Yasuda (Daiichi Sankyo)H-Index: 3
Last. Reiko Kamei (Daiichi Sankyo)H-Index: 1
view all 23 authors...
Trophoblast cell surface antigen 2 (TROP2) is highly expressed on various epithelial tumors and correlates with poor prognosis. We developed the novel TROP2-directed antibody-drug conjugate (ADC), Datopotamab deruxtecan (Dato-DXd, DS-1062a), with a potent DNA topoisomerase I inhibitor (DXd), and evaluated its antitumor activity and safety profiles in preclinical models. The pharmacological activity and mechanism of action of Dato-DXd were investigated in several human cancer cell lines and xenog...
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#1Kenji Iida (Daiichi Sankyo)H-Index: 1
#2Amr H. Abdelhamid Ahmed (Harvard University)
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
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Currently, the only approved treatments for gastrointestinal stromal tumor (GIST) are tyrosine kinase inhibitors (TKIs), which eventually lead to development of secondary resistance mutations in KIT or PDGFRA and disease progression. Herein, we identified G protein-coupled receptor 20 (GPR20) as a novel non-TK target in GIST, developed new GPR20 immunohistochemistry, assessed GPR20 expression in cell lines, PDXs & clinical samples from 2 institutes (USA & Japan). We studied GPR20 expression stra...
3 CitationsSource
#1Takashi Nakada (Daiichi Sankyo)H-Index: 5
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#1Kenji IidaH-Index: 1
#2Amr Hesham Abdelhamid (Harvard University)H-Index: 2
Last. Toshinori AgatsumaH-Index: 12
view all 23 authors...
More than 85% of GISTs are driven by activating mutations in KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Currently, the only approved treatments for GIST are KIT directed tyrosine kinase inhibitors (TKIs). However, treatment with approved TKIs eventually results in disease progression most often due to the development of secondary resistance mutations in KIT. In addition, these agents have limited activity in PDGFRA mutant GIST and...
2 CitationsSource
#1Daisuke Okajima (Daiichi Sankyo)H-Index: 4
#2Junko Yamaguchi (Daiichi Sankyo)H-Index: 5
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 15 authors...
Background: A trophoblast cell surface antigen 2 (TROP2) is a 36-kDa single-pass transmembrane protein overexpressed in various epithelial tumors including non-small cell lung cancer (NSCLC) with relatively low and restricted expression in normal tissues, and is associated with aggressive tumor behavior. Therefore, TROP2 could be an attractive target for cancer therapy. We created DS-1062a, TROP2-targeting antibody-drug conjugate (ADC) with Daiichi Sankyo DXd technology using a novel DNA topoiso...
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#1Satoru Yasuda (Daiichi Sankyo)H-Index: 3
#2Daisuke Okajima (Daiichi Sankyo)H-Index: 4
Last. Masato Murakami (Daiichi Sankyo)H-Index: 1
view all 9 authors...
Background: DS-1062a is a TROP2-targeting antibody-drug conjugate with Daiichi-Sankyo DXd technology. DS-1062a is expected to deliver DXd, a derivative of Exatecan, to TROP2 highly expressed tumors such as epithelial cancers with stronger anti-tumor effect and safer profile than the systemic chemotherapy. SLFN11 has been reported as a sensitivity biomarkers of DNA topoisomerase I inhibitors in several cancers. In this research, we elucidated the potency of combination of TROP2 and SLFN11 as a se...
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#1Hashimoto Yuuri (Daiichi Sankyo)H-Index: 1
#2Kumiko Koyama (Daiichi Sankyo)H-Index: 8
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
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Purpose: HER3 is a compelling target for cancer treatment; however no HER3-targeted therapy is currently clinically available. Here, we produced U3-1402, an anti-HER3 antibody-drug conjugate with a topoisomerase I inhibitor exatecan -derivative (DXd), and systematically investigated its targeted drug delivery potential and antitumor activity in preclinical models. Experimental Design: In vitro pharmacological activities and the mechanisms of action of U3-1402 were assessed in several human cance...
19 CitationsSource
#1Takashi Nakada (Daiichi Sankyo)H-Index: 5
#2Kiyoshi Sugihara (Daiichi Sankyo)H-Index: 4
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 5 authors...
: A major limitation of traditional chemotherapy for cancer is dose-limiting toxicity, caused by the exposure of non-tumor cells to cytotoxic agents. Use of molecular targeted drugs, such as specific kinase inhibitors and monoclonal antibodies, is a possible solution to overcome this limitation and has achieved clinical success so far. Use of an antibody-drug conjugate (ADC) is a rational strategy for improving efficacy and reducing systemic adverse events. ADCs use antibodies selectively to del...
62 CitationsSource
#1Abe Yuki (Daiichi Sankyo)H-Index: 6
#2Takashi Nakada (Daiichi Sankyo)H-Index: 5
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 3 authors...
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#1Abe Yuki (Daiichi Sankyo)H-Index: 6
#2Kiyoshi Sugihara (Daiichi Sankyo)H-Index: 4
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 7 authors...
Antibody–drug conjugates (ADCs) represent a promising class of drugs with a wider therapeutic index (TI) than conventional chemotherapeutic agents due to their efficient and specific drug delivery. ADC payload is attached to antibody by chemical linkage. Two classes of cytotoxins – DNA damaging agents and microtubule inhibitors – have been validated as ADC payloads in clinical trials and four ADCs, MYLOTARG®, ADCETRIS®, KADCYLA®, and BESPONSA®, have been approved so far. There are many different...
1 CitationsSource