Alternative pathway activation in tyrosine kinase inhibitor resistant cancers
My thesis research is engaged in investigating alternative pathways that are turned on in cancers that have become resistant to tyrosine kinase specific small molecule inhibitors. Previous efforts in the lab have shown that in some leukemias, even when a tyrosine kinase that is responsible for tumorigenicity is successfully inhibited with a small molecule inhibitor, downstream pathways are somehow still active. Using new genetic approach, we are attempting to uncover the alternative mechanisms by which resistant cancer cell lines circumvent kinase inhibition and also look for other new pathways that contribute to drug resistance and tumorigenicity. We are looking at leukemias first as a proof of principle, but this strategy will be broadly applied in the future to other small molecule resistant cancers that depend on kinases for their tumorigenesis. Finally, these studies will advocate a departure from using a single small molecule inhibitor in the treatment of cancers and instead argue for the use of a combination of multiple inhibitors for targets of all the pathways discovered by the lentiviral mutagenesis method.