The purpose of the PBS-Bio technology is to make pre-clinical research more predictive of actual patient outcomes. The reasons for the failure of targeted oncology drugs is quite varied and often not well known. Even when the receptor responsible for signaling for the particular tumor is known, a drug that targets this receptor usually is not capable of producing significant responses in most tumors, e.g., EGFR inhibitors ineffective in presence of KRAS mutation, or activation of the PI3K pathway to overcome EGFR blockade.
PBS-Bio technology analyzes primary tumor cell lines' responses to investigational drugs through the use of several types of fluorescent reporters observed over a time-course. Quantification is done by microscopic scanning of cells in culture in multi-well plates using the InCell 3000 laser microscope coupled with robotics that scans a 384 well plate every hour.
Since multiple gene reporters are examined in multiple primary tumor cell types up to 144,000 scans could be required for one drug study. Analysis of these images requires proprietary image processing software running on TGen's 1300 node supercomputer.
After segmenting nuclei and reporter images containing cells, time-course graphs are created showing a real-time picture of the effect of a drug on multiple pathways simultaneously.
This results in a detailed understanding of molecular mechanisms for drug susceptibility and resistance. This also leads to further experiments using combinatorial regimens as well as a means for identifying patients most likely to respond to the investigational drug.
For a more in-depth explanation of the technology, please see the downloadable white paper.