A new study led by a team of researchers from the Garvan Institute of Medical Research in Sydney Australia reveals that utilizing a drug to “soften” pancreatic cancer tumors prior to chemotherapy treatment reduces metastasis in mouse models and doubles survival. Pancreatic cancer has a very low survival rate, with only a handful of treatments for inoperable tumors.
The pancreas is a six-inch, narrow fish-shaped organ that is located behind the stomach, where cancer cells begin to grow. The organ contains two primary types of cells, including endocrine cells, which produce hormones like glucagon and insulin, which is responsible for maintaining blood sugar and exocrine cells that produce enzymes needed for digestion. Most pancreatic cancers develop in the exocrine cells.
Regrettably, pancreatic cancer symptoms are vague and extremely difficult to pin down. Diagnosis most often does not occur until it is advanced, which leaves patients with few treatment options and inoperable tumors.
In over 40 years, the dismal survival rate for pancreatic cancer patients has held strong at just 7 percent.
According to the American Cancer Society, an estimated 53,670 people will be diagnosed with pancreatic cancer and 43,090 people will die of the disease in 2017.
Priming Pancreatic Cancer Tumors
Pancreatic cancer tumors are inoperable, leaving treatment options very limited. Combination chemotherapy is the standard-of-care for the disease, but still this only moderately improves the survival rate.
Since, pancreatic tumors contain a very dense tissue structure, which is extremely difficult for drugs to penetrate, treatment is only further complicated.
The research team utilized mice that were genetically modified to grow pancreatic cancer for this study. The mice were also implanted with pancreatic tumor tissue derived from humans.
The findings reveal that “priming the pancreatic cancer tumors with Fasudil for a full three days prior to combination chemotherapy, survival rates doubled and metastasis was reduced.
Fasudil is believed to stiffed the cells that surround the cancerous tumors and drives cancer progression. In Japan, the drug has been approved for clinically treating stroke.
The researchers note that the drug is capable of temporarily softening the tumor tissue, so it can more easily respond to combination chemotherapy at secondary and primary sites. The drug acts on the stroma, the extremely complex microenvironment of blood vessels, cells and other structures surrounding the cancer cells.
Fasudil “slackens” the structure of the tumor microenvironment, while also making the blood vessels leaky, which in turn improves the standard-of-care treatment, combination chemotherapy.
Innovative intravital microscopy was utilized to observe the effects in real-time.
“We saw the stroma weaken over time and [we] could also see that cancer cells did not spread so readily to secondary sties such as the liver.”
Utilizing quantum dots, the researchers were also able to watch the blood vessels that are responsible for supplying tumors alter over a period of time.
“It was remarkable to watch the quantum dots radiate out from blood vessels adjacent to the tumors after Fasudil treatment, which is an indicator that the vessels have become leaky,” says Dr. Marina Pajic of Garvan’s Kinghorn Cancer Centre.
The study was published in the journal Science Translational Medicine.