Study links genetic variation and resistance to cancer drugs

A new study conducted by a multinational research team has found the reason behind some patients’ failure to respond to several types of cancer drugs. Scientists found a common variation in the BIM gene in people of East Asian descent that contributes to some patients' rejection of Tyrosine kinase inhibitor drugs (TKI). TKI drugs fight certain blood cell cancers, such as chronic myelogenous leukemia (CML), and non-small-cell lung cancers (NSCLC) with mutations in the EGFR gene. Scientists determined how the BIM gene variant caused TKI resistance in cells and devised a strategy to overcome it, explained senior author and associate professor in S. Tiong Ong of the Cancer and Stem Cell Biology at Duke University Medical Center. "A novel class of drugs called the BH3-mimetics provided the answer," Ong added. "When the BH3 drugs were added to the TKI therapy in experiments conducted on cancer cells with the BIM gene variant, we were able to overcome the resistance conferred by the gene. Our next step will be to bring this to clinical trials with patients." Researchers believe the drug resistance occurred because of impaired production of BH3-containing forms of the BIM protein. They say the finding will be good news for those with the BIM gene variant that exists in about 15 percent of the typical East Asian population. People of European or African ancestry do not have this gene variant, the study confirmed. Ong stressed that the next step will be to bring the new strategy to clinical trials with patients. The study was conducted by researchers of the Genome Institute of Singapore (GIS), Singapore General Hospital and the National Cancer Centre Singapore.