Study Finds New Effective Treatment For Pancreatic Cancer
According to new study which was published in today’s issue of Cancer Cell, scientists from Hutchinson Cancer Research Center found a new potential treatment for pancreatic cancer. Pancreatic cancer is one of the deadliest malignancies because it presents symptoms in advance stages, its rapidly spreading to other organs and is very resistant to chemotherapy. The resistance to anti-cancer drugs is explained by the fact that malignant pancreatic tumors build around their self a biological barrier that is impenetrable for chemotherapy drugs. With this study, researchers found a way to penetrate this barrier which can represent a step forward in the treatment of pancreatic cancer.
With this study researchers describe the mechanism which make pancreatic tumors resistant to chemotherapy and a way to break it. This mechanism is represented by a biological barrier that pancreatic cancer builds around its self. After breaking this mechanism, scientists observed that in lab mice models with human pancreatic cancer survival rate has significantly increased. Clinical trials that are using novel chemotherapeutic agents which breake the protection mechanism in pancreatic cancer are conducted by scientists in a few sites in U.S. and Europe.
For this research scientists used lab mouse models with pancreatic ductal adenocarcinomas that were treated with a combination of gemecitabine, the standard chemotherapeutic agent for pancreatic cancer and an enzyme named PEGPH20. When they injected the combination of gemecitabine and PEGPH20, researchers observed that this mixture broke the barrier build by the pancreatic tumors, thus making the chemotherapeutic agent to penetrate into tumor and to spread throughout the malignant tissue. After administration of combination between gemecitabine and PEGPH20, it was observed an increase of 70 percent in mice survival rate, from 55 to 92 days.
“This represents the largest survival increase we’ve seen in any of the studies done in a preclinical model, and it rivals the very best results reported in humans,” researches said.
In their mechanism of acquiring resistance to chemotherapy, pancreatic tumors use a double defense mechanism. First defense mechanism is represented by the fact that pancreatic cancer has a reduced blood supply and for this reason chemotherapy agents are unable to form an efficient concentration in the malignant tissue. The second defense mechanism is represented by the fact that pancreatic tumors posses the ability to create a strong fibroinflammatory response, which include immune cells, fibroblasts and endothelial cells. This cells form an extracellular barrier around the malignant tissue and it also contains a substance called hyaluronan which is made by glycosaminoglycan and is secreted is high levels by pancreatic malignant cells.
Researchers also observed that the result of fibroinflammatory activity of pancreatic cancerous cells is a high amount of interstitial fluid which increase the pressure into malignant tissue, thus making blood vessels that are supplying the tumor to collapse, preventing the malignant tissue to be penetrated by chemotherapy. The main factor the increase pressure into cancer tissue is hyaluronan.
It was observed that by using the combination between gemecitabine and PEGPH20 the levels of hyaluronan begin to rapidly decrease, leading to a reduction of interstitial pressure of pancreatic malignant tissue. This event made the blood vessels that are supplying the tumor to open, thus allowing the chemotherapy agent to reach high concentrations into the malignant tissue and to be more effective.
“Being able to deliver the drugs effectively into the tumor resulted in improved survival as well as the realization that pancreas cancer may be more sensitive to conventional chemotherapy than we previously thought,” researchers added.
Pancreatic ductal adenocarcinoma is a very aggressive type of cancer, being the fourth cause of cancer-related death. From the moment of diagnosis the median survival rate is four to six months and five-year survival rate is less than five percent.