Pancreatic cancer cells have a unique and obscure mechanism of avoiding chemotherapy drugs by attacking the blood vessels that deliver them. Scientists at the University of Pennsylvania reveal answers to help better treat pancreatic cancer in the future.
The type of pancreatic cancer that Duc-Huy Nguyen and his team worked with pancreatic ductal adenocarcinoma or PDAC. It is the common type of pancreatic cancer making up for 95% of diagnoses, according to the Pancreatic Cancer Organization of the UK. When cancer spreads, known as metastasis, it enters the nearby blood vessels, and at this points, the prognosis of the disease is usually fatal. Unfortunately, when the patient is diagnosed with the disease, it already is in this stage. As previously mentioned, the advanced tumors at this stage, show little to know blood vessels infiltrating them, which is how many cancers survive and thrive. Once chemotherapy is introduced, it cannot reach the tumor cells, and thus does not kill them. Nguyen and teamwork to unravel the mystery of the evasive pancreatic cancer.
Using a novel and elegant in-vitro method, known as an “organ on a chip” to mimic the interaction between a pancreatic cancer cell and the blood vessels in the body. At first interaction, the pancreatic cancer cells seemed to recruit blood vessels to the area to help them grow, but hours later the blood vessels started dying and the cancer was growing quickly. To investigate this further, the scientists then used live mice. They found that the endothelial cells of the mice and the in-vitro model were dying and the pancreatic cancer cells were quickly replacing them. They even invaded and replaced the healthy cells within the blood vessel. They found that the activation of ALK7, protein than normally aids in killing cancer cells, and actin, another protein normally found within the body, may somehow aid in PDAC progression as seen in pancreatic cancer.
With this exciting discovery, it gives hope to new, more effective treatments for pancreatic cancer. To learn more about pancreatic cancer, the current treatments, and more, watch this video below:
D.-T. Nguyen et al. A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling. Science Advances. Published online August 28, 2019. DOI: 10.1126/sciadv.aav6789