The research conducted in my laboratory focuses on developing improved protocols for the treatment of cancer. Clinicians have an arsenal of very potent drugs available for treatment of cancer. These drugs, however, lack specificity and often produce severe, life threatening, toxicities. Further, optimal therapeutic effects of any anticancer drug appear to be dependent on their use in a combination setting. Multi-agent therapy is the standard by which cancer is treated. Based on this understanding, research in my laboratory is designing methods and strategies for capturing the benefits of drug combination effects that are often first measured using cell based screening assays. Although basic research interests include evaluation of novel targeted anticancer drugs, my group is also comprehensively pursuing combinations of existing, already approved, cytotoxic agents. The latter studies will provide the proof of concept data needed to demonstrate the value of pursuing anticancer drug combination products. These products will be of particular interest when used with emerging targeted agents, but will also demonstrate the potential to develop new products that may consist of two or more targeted agents.
In order to achieve this, my research group embraces two fundamental principles: (i) drug combination products will be dependent on use of drug carrier technologies and (ii) drug combination products should achieve optimal therapeutic effects using better tolerated drug doses. I have extensive expertise on the use of liposome drug carriers for improving the specificity of anti-cancer drugs as well as enabling the use of some exciting new biologically active agents, such as therapeutically active antibodies, nucleic acid drugs (antisense oligonucleotides and siRNA) and therapeutically active peptides. In general terms, liposomes are small microscopic bags prepared from natural and synthetic lipids (fats). The therapeutic activity of conventional anti-cancer drugs can be improved, sometimes dramatically, when given intravenously trapped inside these lipid bags. Mechanistically, it has been suggested that liposomal drugs deliver more drug to tumors then conventional drug and development of this technology has been based on achieving improvements in drug delivery to sites of cancer growth. It is believed that delivery of liposomal drug carriers from the blood to interstitial sites within the tumor is due to characteristics of tumor blood vessels. In addition, my research clearly establishes that drug release from liposomes, whether in the blood compartment or within the tumor, can increase tumor cell exposure to anticancer drugs. Based on this understanding, my lab is now using drug carriers, such as liposomes, to provide the format to deliver combinations of drugs that are shown, via high content cell screening assays, to interact to achieve better than expect (synergistic) therapeutic activity.