As outlined in a presentation at the American Association for Cancer Research (AACR) Annual Meeting titled,“Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection,” cell function analysis of human tumors provides a novel, real-time view of how such tumors act within their natural microenvironment. This information can, in turn, accelerate the drug development process and improve clinical therapy.
Led by Robert Nagourney, MD, medical director of Rational Therapeutics and the Todd Cancer Institute at Long Beach Memorial Medical Center, the investigators have applied a human tumor micro-spheroid platform that measures both apoptotic and non-apoptotic cell death events and other cellular responses following exposure to a variety of agents.
With its capacity to measure genetic and epigenetic events, the platform provides a functional, real-time adjunct to static genomic and proteomic platforms. By examining small clusters of cancer cells [microspheroids or microclusters] in their native state, they provide a snapshot of the response of tumor cells to drugs, combinations and targeted therapies.
The analysis is unique in that each micro-spheroid examined contains all the complex elements of tumor bio-systems found in the human body and have a major impact on clinical response. Cell function analysis is a conduit that connects novel drugs to clinicians and patients in need. Appropriate use of this platform has the potential to save the pharmaceutical industry millions of dollars, shave years off the drug development cycle and improve clinical therapy.
There are any number of variable that affect drugs, including the rate of excretion of the drugs by the kidneys and liver, protein binding and a myriad of other biological factors. In the body, these cells interact with and are supported by other living cells, both malignant and non-malignant cells. That is why cell-death functional profiling assays study cancer cells in microspheroids-microclusters.
Three-dimensional (3D) tissue culture methods have an invaluable role in tumor biology and provides very important insights into cancer biology. As well as increasing our understanding of homeostasis, cellular differentiation and tissue organization, they provide a well defined environment for cancer research in contrast to the complex host environment of an in vivo model.
Due to their enormous potential, 3D tumor cultures are currently being exploited by many branches of biomedical science with therapeutically orientated studies becoming the major focus of research. Recent advances in 3D culture and tissue engineering techniques have enabled the development of more complex heterologous 3D tumor models.