BACKGROUND:  While considerable progress has been made towards the diagnosis and treatment of a plethora of cancers, very few inroads have been made with respect to pancreatic cancer. As the 5th leading cause of cancer-related deaths in the U.S. it is among the most devastating. Indeed, pancreatic cancer is difficult to diagnose, is largely untreatable and is highly metastatic. Thus the need for sufficient technology with which to combat the disease is self-evident. Unfortunately current clinical protocols for the diagnosis and treatment of pancreatic cancer have been met with little, if any, success.

INNOVATION:   Researchers at UCLA have identified a novel approach for the treatment of pancreatic cancer by down-regulating cellular survival factors while concomitantly inducing apoptosis (cell death). The simultaneous administration of plant-derived polyphenolic compounds with inhibitors of reactive oxygen species (ROS) was found to act synergistically to inhibit pancreatic cancer growth and tumor metastasis. Interestingly, one particular polyphenol, rottlerin, exhibited increased potency without the need for ROS-inhibitors. In vivo studies in mice using polyphenols revealed that pancreatic cancer cells selectively underwent apoptosis while non-diseased tissue was unaffected. Experimental evidence has revealed NF-kB, PI 3-kinase and ROS-generators as cell survival targets that are attenuated in this approach. In contrast, the mitochondrial permeability transition pore and caspases have been identified as molecular targets that are responsible for triggering apoptosis. This discovery can potentially be used for the treatment of other cancers, as well as for sensitizing refractory tumors to chemotherapeutic and/or radiation therapies.

ADVANTAGES

• A combination of polyphenols and ROS inhibitors dramatically reduces tumor size and inhibits tumor metastasis in a pancreatic cancer mouse model.
• The polyphenol rottlerin is effective without added ROS inhibitors.
• Non-diseased tissue is unaffected in in vivo studies in mice.
• There is no immunological response since cells die via apoptosis.
• There is no apparent toxicity.

APPLICATIONS

• Potential treatment for pancreatic cancer.
• Potential to sensitize refractory cancer cells to other treatments.
• May be applicable to other cancers.
• Possible utility as a preventative for pancreatic cancer.

Related Papers (Selected)

Mouria M, Gukovskaya AS, Jung Y, Buechler P, Hines OJ, Reber HA, Pandol SJ. Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. Int J Cancer. 2002 Apr 10;98(5):761-9 [more...]