One of the most dangerous forms of cancer, pancreatic ductal adenocarcinoma, can often be synonymous with a death sentence, given that it is difficult to detect before it has reached its advanced stage, and current treatment options are not nearly effective enough. Pancreatic ductal tumors are surrounded by structural elements called stroma, made up of many substances, including connective tissue and pericyte cells, which block chemotherapy drugs from effectively reaching the cancerous cells through pancreatic blood vessels. The team led by Drs. Andre Nel and Huan Meng of UCLA’s Jonsson Comprehensive Cancer Center has developed what they believe will be a 1- 2- punch in the fight against pancreatic cancer.
The approach consists of two stages of nanoparticle treatment: a preliminary treatment consisting of nanoparticles which clear the stroma, opening up access to the cancerous cells for the second treatment consisting of chemotherapy nanoparticles. The preliminary wave of nanoparticles functions by inhibiting the signaling pathways in the pericytes responsible for their attraction to the tumor blood vessels, clearing the way for the second wave, containing traditional chemotherapy, for targeted delivery to the tumor.
“To test this nanotherapy, the researchers used immuno-compromised mice in which they grew human pancreatic tumors called xenografts under the skin. With the two-wave method, the xenograft tumors had a significantly higher rate of shrinkage than tumors exposed only to chemotherapy given as a free drug or carried in nanoparticles without first-wave treatment.
“This two-wave nanotherapy is an existing example of how we seek to improve the delivery of chemotherapy drugs to their intended targets using nanotechnology to provide an engineered approach,” said Nel, chief of UCLA’s division of nanomedicine. “It shows how the physical and chemical principles of nanotechnology can be integrated with the biological sciences to help cancer patients by increasing the effectiveness of chemotherapy while also reducing side effects and toxicity. This two-wave treatment approach can also address biological impediments in nanotherapies for other types of cancer.”
The research was funded by the U.S. Public Health Service and the National Cancer Institute.”