San Antonio-based cancer therapeutics nanotechnology platform developer Azaya Therapeutics Inc. recently announced a research collaboration with the University of Chicago Ludwig Center for Metastasis Research, led by investigators Stephen J. Kron MD-PhD and Ralph R. Weichselbaum MD, in exploring the efficacy of its pipeline investigational drug ATI-1123. ATI-1123 is a generic formulation of the FDA approved chemotherapy agent docetaxel, (market name: Taxotere), in treating experimentally formed tumors in mice using very low intensity and clinically-safe radiation. Another observation to be made during the study is whether the combination of ATI-1123 and docetaxel could be beneficial in combination in treating already irradiated tumors.
The technology to be used in this case is the Protein Stabilized Liposome (PSL) which is patented by Azaya Therapeutics. Liposomes are phospholipid bilayer molecules that have been the focus of drug delivery systems for quite some time. The drug is encapsulated within these bilayered molecules, and administered systemically to act on the target cells and/or organs. Using PSL techniques for the administration of chemotherapeutic and anti-cancer drugs can help in protecting the ‘normal’ cells from the toxic effects of these drugs (as they target the cell division, growth and replication of cells) and make the drug more effective by ensuring selective action on target cells. Some other benefits of using liposomal drug delivery systems include better pharmacokinetics, enhanced blood-circulation time and most importantly reducing their concentration in vulnerable tissues like those in the liver and kidneys, hence reducing their toxic side effects (hair fall, nausea, fatigue, irritation, etc.). It is because of these toxic effects that chemotherapy in the conventional form is discontinued in patients before its effects can be exerted to the maximum. Liposomal drug delivery system has the potential to overcome these shortcomings.
Another aspect of liposomal chemotherapeutic treatment comes in the form of blood vessels associated with tumor cells which lack the strength and rigidity of those associated with normal vasculature. This makes blood leak into the tumor cells, and hence the liposomal chemical can exert its effect on the target (tumor) cells. This phenomenon is referred to as enhanced permeability and retention (EPR) effect.
Recent research at the University of Chicago has suggested the combination of liposomal chemotherapy in combination with radiotherapy can actually enhance the effects of the drugs on the target cells with more specificity. This would prove all the more useful in case of docetaxel , which although is a proven drug with a very high efficiency, has its use cut short because of its toxicity on the normal cells. The ATI-1123 liposomal encapsulation of docetaxel is thus aimed at providing more specified and less toxic treatment options for cancer patients. Radiation is expected to enhance the effects, synergistically with chemotherapy.
“The outcome of this study could lead to a new treatment option for cancer patients in which our ATI-1123 liposomal docetaxel could provide a powerful means to improve the benefits of radiotherapy,” said Mike Dwyer, President and CEO of Azaya. “Given the established safety of ATI-1123 on its own, we plan to test this combination in cancer patients if the results of the animal study are promising,” he added.