Adjuvant treatment of pancreatic cancer in 2009: where are we? Highlights from the 45th ASCO annual meeting. Orlando, FL, USA. May 29-June 2, 2009.

JOP. 2009;10(4):373-7

Authors: Saif MW

Despite attempted curative resection of localized pancreatic adenocarcinoma, most patients succumb a recurrence and die of their disease. The Gastrointestinal Tumor Study Group, European Organization for Research and Treatment of Cancer, and European Study Group for Pancreatic Cancer trials have suggested the benefit of adjuvant therapy. However, the relatively few randomized trials available have not established a definite standard of care due to study limitations. Although these trials, and the recently published Charité Onkologie (CONKO)-001 trial, have shown a definite advantage of adjuvant chemotherapy, the most effective chemotherapy and the role of radiation therapy remain unclear. This review will discuss the data available from reported trials of adjuvant therapy in pancreatic cancer, especially the results of the ESPAC-3 study presented at the annual meeting of ASCO 2009, and consider future directions for clinical trials.

PMID: 19581737 [PubMed - in process]

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Characterization of Novel Diaryloxazole-Based Compounds as Potential Agents to Treat Pancreas Cancer.

J Pharmacol Exp Ther. 2009 Aug 5;

Authors: Shaw A, Henderson MC, Flynn G, Samulitis B, Han H, Stratton S, Chow HH, Hurley LH, Dorr RT

A series of diaryl- and fluorenone-based analogs of a lead compound UA-62784 was synthesized with the intention of improving upon the selective cytotoxicity of UA-62784 against human pancreatic cancer cell lines with a deletion of the tumor suppressor gene DPC-4 (SMAD-4). Over 80 analogs were synthesized and tested for antitumor activity against pancreatic cancer (PC) cell lines (the PC series). Despite a structural relationship to UA-62784 which inhibits the mitotic kinesin centromere protein E (CENP-E), none of the analogs was selective for DPC-4-deleted pancreatic cancer cell lines. Furthermore, none of the analogs was a potent or selective inhibitor of 4 different mitotic kinesins (Eg5, CENP-E, MKLP-1, MCAK). Therefore, other potential mechanisms of action were evaluated. A diaryloxazole lead analog from this series, PC-046, was shown to potently inhibit several protein kinases that are over-expressed in human pancreatic cancers, including TrkB, IRAK4 and PIM-1. Cells exposed to PC-046 exhibit a cell cycle block in S-phase followed by apoptotic death and necrosis. PC-046 effectively reduced MiaPaca-2 tumor growth in SCID mice by 80% compared to untreated controls. The plasma half-life was 7.5h and cytotoxic drug concentrations of > 3 microM were achieved in vivo in mice. The diaryloxazole series of compounds represent a new chemical class of anti-cancer agents that inhibit several types of cancer-relevant protein kinases. PMID: 19657049 [PubMed - as supplied by publisher]

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