By correlating the responses of these cells to targeted therapeutic drugs, the researchers were able to identify the molecular characteristics of cells that were most sensitive to the drugs. They tested their approach by analyzing responses of the cell line panel to lapatinib, a duel inhibitor of EGFR and ErbB2 and CI-1040, a MEK enzyme inhibitor. These studies defined molecular signatures that predicted individual responses among the cell lines to the drugs. For Lapatinib, the strongest correlate of response was amplification and over expression of ErBB2, consistent with clinical experience. For CI-1040, changes in the MEK pathway were most strongly associated with response. Predictors based on combinations of molecular correlates of response were able to quantitatively predict individual cell line responses.
"The concordance of our markers of response to lapatinib with those observed clinically suggests that the molecular markers identified in the cell line collection can be used to guide the use and testing of other approved and experimental drugs," Gray said. "This is important since it is logistically and financially impossible to test all of the experimental medicines in each cancer subtype. This ‘systems?approach suggests a way to prioritize drugs for use in patients and for initial clinical tests."
According to Gray, a large of number of emerging therapeutic agents should be prioritized for testing in the subtypes of breast cancer along with other cancers and their subtypes. When therapies are ineffective, they may produce harmful side effects and decrease a patient’s quality of life.
KRAS mutation in colorectal cancer is a predictive factor of response and progression free survival in patients treated with Cetuximab: Abstract 5671
Mutations in the KRAS oncogene could predict a lack of response to the drug cetuximab in patie
Source:American Association for Cancer Research