Imagine millions of cancer cells organized in thousands of small divots. Hit these cells with drugs and when some cells die, you have a candidate for a cancer drug. But a review published this week in the journal Expert Opinion on Drug Discovery argues that these 2D models in fact offer very little information about a potential drug's effects in the body and may often give researchers misleading results.
"Up until the 1980s animal models were the standard for cancer drug discovery. However, with the increase in the number of compounds available for testing and the advent of high-throughput screening (HTS), the use of animals to discover cancer drugs became too costly and unethical. Consequently, 2D cell culture models have become the mainstay for drug discovery or to explore a drug's mechanism of action," says Dan LaBarbera, PhD, investigator at the University of Colorado Cancer Center and the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences. LaBarbera is principal investigator of the recent review, on which he collaborated with Skaggs colleagues Brian Reid, PhD, and Byong Hoon Yoo, PhD.
LaBarbera cites the gap between results in 2D cells and effects in tumors themselves as a contributing factor for the declining rate of drugs passing FDA approval. In particular, only 5 percent of investigational new drugs targeting cancer make it through clinical trials, at a cost of about $800 million per drug. When you factor in the inevitable failures at various points in development, each approved drug costs an average $1.5 billion.
To increase the drug success rate, LaBarbera suggests something called the multicellular tumor spheroid (MCTS) model. In these models, instead of 2D monolayers, cancer cells are cultured as 3D spheroids. One of the advantages of the MCTS model is that when spheroids reach a critical diameter, they begin to form an outer proliferating zone, an inner quiescent zone, and a central necr
|Contact: Garth Sundem|
University of Colorado Denver