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Chauhan, Dharminder; Tian, Ze; Nicholson, Benjamin; Kumar, K.G. Suresh; Zhou, Bin; Carrasco, Ruben; McDermott, Jeffrey L.; Leach, Craig A.; Fulcinniti, Mariaterresa; Kodrasov, Matthew P.; Weinstock, Joseph; Kingsbury, William D.; Hideshima, Teru; Shah, Parantu K.; Minvielle, Stephane; Altun, Mikael; Kessler, Benedikt M.; Orlowski, Robert; Richardson, Paul; Munshi, Nikhil; Anderson, Kenneth C.
Cancer cell, 09/2012, Letnik: 22, Številka: 3Journal Article
Bortezomib therapy has proven successful for the treatment of relapsed/refractory, relapsed, and newly diagnosed multiple myeloma (MM); however, dose-limiting toxicities and the development of resistance limit its long-term utility. Here, we show that P5091 is an inhibitor of deubiquitylating enzyme USP7, which induces apoptosis in MM cells resistant to conventional and bortezomib therapies. Biochemical and genetic studies show that blockade of HDM2 and p21 abrogates P5091-induced cytotoxicity. In animal tumor model studies, P5091 is well tolerated, inhibits tumor growth, and prolongs survival. Combining P5091 with lenalidomide, HDAC inhibitor SAHA, or dexamethasone triggers synergistic anti-MM activity. Our preclinical study therefore supports clinical evaluation of USP7 inhibitor, alone or in combination, as a potential MM therapy. ► P5091 is a potent and selective inhibitor of deubiquitylating enzyme USP7 ► P5091 triggers in vitro and in vivo antimyeloma activity ► P5091 activates HDM2/p53/p21 signaling axis ► Synergistic anti-MM activity of P5091 with SAHA, lenalidomide, or dexamethasone
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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