Drug action in pancreatic cancer tracked and improved by nanotechnology
Tiny biosensors used with new advanced imaging techniques are markedly improving drug targeting of solid tumors, according to new research. These new technologies work in real time and in three dimensions. They can show how cancers spread and how active cancer cells respond to a particular drug. They can also indicate how much, how often, and how long to administer drugs. Preclinical models of the disease can allow them to guide the use of combination therapies that enhance drug delivery by breaking up the tissue surrounding a tumor.
The signaling protein Src, which becomes activated and drives invasive pancreatic cancer, was examined in this study. The study also examined how dasatinib, which is currently in phase II clinical trials, could deactivate Src.
“We have already shown that Src is activated in pancreatic tumors and we knew that dasatinib deactivates Src and could partially reduce the spread of this form of cancer. Through a collaborative partner in the US, we had access to FRET (fluorescence resonance energy transfer) imaging technology,” said Paul Timpson, PhD, of the Garvan Institute of Medical Research in Sydney, Australia.
Studies of tumor signaling have been limited to two dimensional and lacked dynamic reporting on targeted drug therapy in live tumor tissue. Nanotechnology opens a portal that allows researchers to watch cancer metastasize and to determine where in the tumor to direct targeted drug therapy.
FRET enables mapping of highly aggressive areas and regions in which drug delivery is poor deep within a tumor. The imaging technology can identify where improvements in drug delivery are needed to improve clinical outcome.
Pancreatic tumors are difficult to treat because they are extremely dense with collagen and have poor blood vessel networks for drug delivery.
Co-author Kurt Anderson, PhD, of the Beatson Institute for Cancer Research in Glasgow, United Kingdom, observed that combination therapies can be used to break down collagen, weakening tumor architecture and making it easier to get the drugs where they need to be. “The trick is to break down the structure just enough to get the drug in, but not so much that you damage the organ itself,” Anderson said. “These new FRET technologies help us gauge what is just enough and not too much.”The researchers findings were published in Cancer Research (2013; doi:10.1158/0008-5472.CAN-12-4545).