Strimpakos Alexios S, Syrigos Konstantinos N, Saif Muhammad Wasif
Oncology Unit, Sotiria General Hospital, University of Athens, Athens, Greece.
JOP. 2010 Mar 5;11(2):124-7.
Pancreatic cancer is an aggressive type of cancer ranking as the 10th most common cancer and the 4th cause of cancer related deaths. Due to disappointing treatment results and outcome of pancreatic cancer patients there is urgent need for better understanding of pathogenesis, mechanisms of tumor progression and resistance to treatment in order to achieve etiological approach. The development of the field of translational research and pharmacogenomics during the last several years has revealed many molecular pathways being aberrant in pancreatic cancer. This knowledge has led to the identification of biomarkers with prognostic or predictive value and the development of novel drugs against specific abnormal targets of pancreatic tumors. In this year's ASCO Gastrointestinal Cancers Symposium, researchers presented data showing evidence of biomarkers with prognostic value (Abstracts #166, #140, and #126) and genetic polymorphisms predicting possibly efficacy of gemcitabine treatment (Abstract #166). The development of the new small molecule CRT0066101 targeting the protein kinase D (PKD), which is upregulated significantly in pancreatic cancer cells was also presented (Abstract #159). This small molecule blocked specifically PKD and inhibited potently in vitro and in vivo the growth of pancreatic cancer cells. Furthermore, a retrospective analysis of KRAS status on resected pancreatic cancer specimens showed that frequency of KRAS mutations was 67% (57% of those were on codon 12), lower than previous reported in more advanced stages (Abstract #169). In this paper we present details and comment on these works.
胰腺癌是一种侵袭性癌症，是第10大常见癌症，也是癌症相关死亡的第4大原因。由于胰腺癌患者的治疗结果和预后令人失望，迫切需要更好地了解其发病机制、肿瘤进展机制和对治疗的耐药性，以便采取病因学方法。在过去几年中，转化研究和药物基因组学领域的发展揭示了胰腺癌中许多异常的分子途径。这些知识促使人们识别出具有预后或预测价值的生物标志物，并开发出针对胰腺肿瘤特定异常靶点的新型药物。在今年的美国临床肿瘤学会胃肠癌研讨会上，研究人员展示的数据表明存在具有预后价值的生物标志物（摘要#166、#140和#126）以及预测吉西他滨治疗可能疗效的基因多态性（摘要#166）。还展示了一种靶向蛋白激酶D（PKD）的新型小分子CRT0066101的研发情况，PKD在胰腺癌细胞中显著上调（摘要#159）。这种小分子特异性阻断PKD，并在体外和体内有效抑制胰腺癌细胞的生长。此外，一项对切除的胰腺癌标本的KRAS状态的回顾性分析表明，KRAS突变频率为67%（其中57%发生在密码子12），低于先前报道的更晚期阶段（摘要#169）。在本文中，我们将详细介绍并评论这些研究成果。
