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Feed-forward alpha particle radiotherapy ablates androgen receptor-addicted prostate cancer
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- McDevitt, Michael R. (author)
- Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
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- Thorek, Daniel L.J. (author)
- Johns Hopkins University School of Medicine
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- Hashimoto, Takeshi (author)
- Tokyo Medical University
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- Gondo, Tatsuo (author)
- Tokyo Medical University
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- Veach, Darren R. (author)
- Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
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- Sharma, Sai Kiran (author)
- Memorial Sloan-Kettering Cancer Center
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- Kalidindi, Teja Muralidhar (author)
- Memorial Sloan-Kettering Cancer Center
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- Abou, Diane S. (author)
- Johns Hopkins University School of Medicine
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- Watson, Philip A. (author)
- Memorial Sloan-Kettering Cancer Center
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- Beattie, Bradley J. (author)
- Memorial Sloan-Kettering Cancer Center
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- Timmermand, Oskar Vilhemsson (author)
- Lund University,Lunds universitet,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,Systemic Radiation Therapy Group,Lund University Research Groups
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- Strand, Sven Erik (author)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Lewis, Jason S. (author)
- Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
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- Scardino, Peter T. (author)
- Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
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- Scher, Howard I. (author)
- Memorial Sloan-Kettering Cancer Center,Weill Cornell Medical College
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- Lilja, Hans (author)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups,University of Oxford,Memorial Sloan-Kettering Cancer Center
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- Larson, Steven M. (author)
- Memorial Sloan-Kettering Cancer Center,Weill Cornell Medical College
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- Ulmert, David (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Memorial Sloan-Kettering Cancer Center
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(creator_code:org_t)
- 2018-04-24
- 2018
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
- Related links:
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
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- Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa. Alpha-particle irradiation of PCa is prompted by molecularly specific-targeting and internalization of the humanized monoclonal antibody hu11B6 targeting hK2 and further accelerated by inherent DNA-repair that up-regulate hK2 (KLK2) expression in vivo. hu11B6 demonstrates exquisite targeting specificity for KLK2. A single administration of actinium-225 labeled hu11B6 eradicates disease and significantly prolongs survival in animal models. DNA damage arising from alpha particle irradiation induces AR and subsequently KLK2, generating a unique feed-forward mechanism, which increases binding of hu11B6. Imaging data in nonhuman primates support the possibility of utilizing hu11B6 in man.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Fysik -- Annan fysik (hsv//swe)
- NATURAL SCIENCES -- Physical Sciences -- Other Physics Topics (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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McDevitt, Michae ...
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Thorek, Daniel L ...
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Hashimoto, Takes ...
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Gondo, Tatsuo
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Veach, Darren R.
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Sharma, Sai Kira ...
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show more...
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Kalidindi, Teja ...
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Abou, Diane S.
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Watson, Philip A ...
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Beattie, Bradley ...
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Timmermand, Oska ...
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Strand, Sven Eri ...
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Lewis, Jason S.
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Scardino, Peter ...
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Scher, Howard I.
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Lilja, Hans
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Larson, Steven M ...
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Ulmert, David
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Physical Science ...
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and Other Physics To ...
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Lund University