Purpose of review Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer with distinct molecular pathogenesis. This review summarizes the rationale behind current clinical approaches, as well as advances made in 2012 toward the elucidation of underlying pathway aberrations and development of targeted therapies that exploit these unique characteristics. Recent findings Within the last year, exome-wide analyses have highlighted key mutations to guide rational drug design. The PI3/AKT/mTOR pathway and regulators of cell cycle such as cyclin E/F-box proteins appear to be particularly important. Understanding the epithelial to mesenchymal transition may explain the aggressive pattern of spread frequently observed in this disease. There is heightened evidence for heritable syndromes in association with USC. Conflicting retrospective data continue to emerge regarding optimal therapy, especially for early-stage disease, although prospective studies are underway. Immunotherapies targeting Her2/Neu and vascular endothelial growth factor remain an area of active research. Upregulation of class III beta-tubulin observed in paclitaxel-resistant disease may identify candidates for therapy with novel microtubule-stabilizing agents such as epothilones. Summary There is an expanding role for contemporary novel approaches in the treatment of USC. The results of clinical investigations using new target antigens, epothilones, and small molecule inhibitors are eagerly awaited.
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Johns Hopkins Med Inst, Dept Gynecol & Obstet, Div Gynecol Oncol, Baltimore, MD 21205 USAJohns Hopkins Med Inst, Dept Gynecol & Obstet, Div Gynecol Oncol, Baltimore, MD 21205 USA
Fader, Amanda Nickles
Santin, Alessandro D.
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Yale Univ, Sch Med, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USAJohns Hopkins Med Inst, Dept Gynecol & Obstet, Div Gynecol Oncol, Baltimore, MD 21205 USA
Santin, Alessandro D.
Gehrig, Paola A.
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Univ N Carolina, Div Gynecol Oncol, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USAJohns Hopkins Med Inst, Dept Gynecol & Obstet, Div Gynecol Oncol, Baltimore, MD 21205 USA
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Technion Israel Inst Technol, Rappaport Fac Med, Carmel Med Ctr, Haifa, IsraelFdn IRCCS Ist Nazl Tumori Milano, Milan, Italy
Segev, Yakir
Kim, Se Ik
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Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul 03080, South KoreaFdn IRCCS Ist Nazl Tumori Milano, Milan, Italy
Kim, Se Ik
dos Reis, Francisco J. Candido
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Univ Sao Paulo, Dept Gynecol & Obstet, Ribeirao Preto Med Sch, Sao Paulo, BrazilFdn IRCCS Ist Nazl Tumori Milano, Milan, Italy
dos Reis, Francisco J. Candido
Lopez, Salvatore
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Fdn IRCCS Ist Nazl Tumori Milano, Milan, ItalyFdn IRCCS Ist Nazl Tumori Milano, Milan, Italy
Lopez, Salvatore
Mariani, Andrea
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Mayo Clin, Dept Obstet & Gynecol, Rochester, MN USAFdn IRCCS Ist Nazl Tumori Milano, Milan, Italy
Mariani, Andrea
Leitao, Mario M., Jr.
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Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA
Cornell Univ, Joan & Sanford I Weill Med Coll, New York, NY 10021 USAFdn IRCCS Ist Nazl Tumori Milano, Milan, Italy
Leitao, Mario M., Jr.
Raspagliesi, Francesco
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Fdn IRCCS Ist Nazl Tumori Milano, Milan, ItalyFdn IRCCS Ist Nazl Tumori Milano, Milan, Italy