Laboratory of Experimental Endocrinology, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Curr Cancer Drug Targets. 2013 May;13(4):460-71. doi: 10.2174/1568009611313040008.
Pancreas cancer is the fourth leading cause of cancer death due to the limited treatment success rate. The wide number of signalling pathway aberrations contributing to tumorigenesis, progression and drug resistance, is the main reason for unsuccessful treatments in pancreatic cancer. An additional and still under-investigated intracellular cancer target is the peroxisome proliferator activated receptor gamma (PPAR-γ). Several studies have shown the in vitro antitumor activity of PPAR-γ agonists in cancer cells but, if used in monotherapy, they were poorly effective in cancer treatment. The present review will focus on the potential therapeutic role of PPAR-γ agonists in combination with other drugs (type I interferons, gemcitabine and COX-2 inhibitors), highlighting molecular interactions and signalling pathways involved in pancreatic cancer cells. Understanding of the underlying molecular mechanisms and survival pathways activated in cancer cells should promote the development of more successful strategies based on the specific targeting of molecular pathways involved in the resistance to anti-cancer agents.
胰腺癌是癌症死亡的第四大主要原因，这是由于治疗成功率有限。导致肿瘤发生、进展和耐药的信号通路异常广泛，是胰腺癌治疗失败的主要原因。另一个尚未深入研究的细胞内癌症靶点是过氧化物酶体增殖物激活受体γ（PPAR-γ）。多项研究表明，PPAR-γ 激动剂在癌细胞中的体外抗肿瘤活性，但如果单独使用，在癌症治疗中的效果很差。本综述将重点讨论 PPAR-γ 激动剂与其他药物（I 型干扰素、吉西他滨和 COX-2 抑制剂）联合应用的潜在治疗作用，强调涉及胰腺癌细胞的分子相互作用和信号通路。对癌细胞中激活的潜在分子机制和存活途径的了解，应促进基于针对涉及抗癌药物耐药性的分子途径的特异性靶向的更成功策略的发展。
