Conceptual framework for cutting the pancreatic cancer fuel supply.
Conceptual framework for cutting the pancreatic cancer fuel supply.
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DOI：
10.1158/1078-0432.ccr-12-0041
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发表时间：
2012-08-15
期刊：
影响因子：
--
通讯作者：
Dang CV
中科院分区：
文献类型：
--
作者：
Le A;Rajeshkumar NV;Maitra A;Dang CV
尽管治疗方法不断改进，胰腺导管腺癌（又称胰腺癌）仍然是最令人恐惧和临床上最具挑战性的疾病之一。胰腺癌的遗传图谱表明 KRAS 激活突变几乎无处不在，CDKN2A、SMAD4 和 TP53 反复失活突变。迄今为止，开发针对 KRAS 特异性杀死癌细胞的药物的尝试一直令人失望。在这方面，对胰腺癌细胞代谢紊乱的了解可能会带来新的治疗方法。与其他癌症一样，胰腺癌细胞依赖燃料来源来维持体内平衡和增殖。因此，中断两种主要营养素（葡萄糖和谷氨酰胺）的使用可能会提供新的治疗途径。此外，KRAS 突变胰腺癌已被证明依赖于自噬，并且在临床前环境中抑制自噬已显示出希望。在此，回顾了阻断胰腺燃料供应的概念框架。
Pancreatic ductal adenocarcinoma (a.k.a. pancreatic cancer) remains one of the most feared and clinically challenging diseases to treat despite continuous improvements in therapies. The genetic landscape of pancreatic cancer demonstrates near ubiquitous activating mutations of KRAS, and recurrent inactivating mutations of CDKN2A, SMAD4 and TP53. To date, attempts to develop agents to target KRAS to specifically kill cancer cells has been disappointing. In this regard, an understanding of cellular metabolic derangements in pancreatic cancer could lead to novel therapeutic approaches. Like other cancers, pancreatic cancer cells rely on fuel sources for homeostasis and proliferation; as such, interrupting the use of two major nutrients, glucose and glutamine, may provide new therapeutic avenues. In addition, KRAS-mutant pancreatic cancers have been documented to depend on autophagy, and the inhibition of autophagy in the preclinical setting has shown promise. Herein, the conceptual framework for blocking the pancreatic fuel supply is reviewed.