Cancer Research
Research Toward a Cure
Self-sufficiency in Growth Signals
Self-sufficiency in growth signals is one of the six hallmarks of cancer cells. This generally happens when the normal growth signals from tissues and other cells are either not received or needed by the self-sufficient cells. These cells either produce growth hormones or appear to inherently possess a growth stimulus to drive uncontrolled cell division.
Cell Proliferation Assay on Odyssey® Infrared Imaging System
Dr. Daniel Haber's team at Massachusetts General Hospital in Boston is studying the response of non-small cell lung cancer (NSCLC) to tyrosine kinase inhibitors such as gefitinib and erlotinib. NSCLC patients often respond to these drugs initially, but relapse due to acquired resistance caused by a mutation in the Epidermal Growth Factor Receptor (EGFR) kinase domain.
[ABOVE] Acquired HKI-272 resistance in PC9 NSCLC cells.
Dose-dependent growth inhibition of PC9 cells and HKI-272
resistant cells, measured by DNA staining with Odyssey Infrared Imager.
Studying the occurrence of the same phenomenon with the irreversible kinase inhibitor, HKI-272, the research team ran an assay by plating 3,000 cells/well (PC9 NSCLC cells) in a 96-well plate in the presence of various concentrations of drugs. After 72 hours, they fixed and stained the cells with Syto® 60 DNA stain and performed fluorescence imaging. The graph (right) shows that parental PC9 cells (red line) are sensitive to the drug showing complete growth inhibition at drug concentration of 10-7M. However, stably drug resistant clones (Clones 19, 23, 37, 47 and 49) do develop, and a much higher drug concentration (10-6M) is needed for complete growth inhibition.
Reprinted with permission from Mol Cancer Ther. 7(4); 874-9 (2008)
