New class of proteins allows breast cancer cells to evade tyrosine kinase inhibitors

Researchers believe that the cancer cells escape TKIs by circumventing the RTKs and utilizing other enzymes that are not TKI-sensitive.

In the current issue of the Journal of Clinical Investigation, two groups identify a pair of related oncogenes, FAM83A and B, which allow breast cancer cells to survive TKI treatment. Researchers led by Mina Bissell at the Lawrence Berkeley National Laboratory in Berkeley, CA performed a screen of human breast cancer cell lines to identify genes that make cancer cells resistant to EGFR TKIs. Bissell and colleagues determined that increased expression of FAM83A increases proliferation and invasion, while decreased expression delays tumor growth in mice and renders cancer cells sensitive to TKIs.

At Case Western Reserve Medical School in Cleveland, OH, Mark Jackson and colleagues identified FAM83B as a gene that allows normal human mammary cells to become malignant. Further, expression of FAM83A and B in human tumors was correlated with decreased overall survival. Taken together, these studies identify two genes that may serve as novel therapeutic targets. In a companion piece, Steven Grant of the Medical College of Virginia discusses the impact of this research on the development of strategies to overcome resistance to currently available TKIs.