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Feed-forward alpha particle radiotherapy ablates androgen receptor-addicted prostate cancer

McDevitt, Michael R. (author)
Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
Thorek, Daniel L.J. (author)
Johns Hopkins University School of Medicine
Hashimoto, Takeshi (author)
Tokyo Medical University
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Gondo, Tatsuo (author)
Tokyo Medical University
Veach, Darren R. (author)
Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
Sharma, Sai Kiran (author)
Memorial Sloan-Kettering Cancer Center
Kalidindi, Teja Muralidhar (author)
Memorial Sloan-Kettering Cancer Center
Abou, Diane S. (author)
Johns Hopkins University School of Medicine
Watson, Philip A. (author)
Memorial Sloan-Kettering Cancer Center
Beattie, Bradley J. (author)
Memorial Sloan-Kettering Cancer Center
Timmermand, Oskar Vilhemsson (author)
Lund University,Lunds universitet,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,Systemic Radiation Therapy Group,Lund University Research Groups
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
Lewis, Jason S. (author)
Memorial Sloan-Kettering Cancer Center,Weill Cornell Medical College
Scardino, Peter T. (author)
Memorial Sloan-Kettering Cancer Center,Weill Cornell Medical College
Scher, Howard I. (author)
Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
Lilja, Hans (author)
Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups,Memorial Sloan-Kettering Cancer Center,University of Oxford
Larson, Steven M. (author)
Memorial Sloan-Kettering Cancer Center,Weill Cornell Medical College
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.
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
Related links:
http://dx.doi.org/10... (free)
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https://www.nature.c...
https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
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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