2022 LCRF–ALK Positive Research Grant
Álvaro Villalonga, PhD
Memorial Sloan-Kettering Cancer Center
Identifying epigenomic mechanisms of ALK TKI resistance
ALK inhibitors are very effective in the treatment of ALK fusion-positive tumors, but these eventually develop resistance to therapy. Understanding how tumors become resistant is key to identify subsequent therapeutic approaches that will extend treatment efficacy. Most of what we know about treatment resistance in this setting is limited to how some of these tumors develop other changes in the ALK gene itself or other genes (mutations). However, other tumors may become resistant through a different way, by undergoing major shifts in which genes are active (“epigenetic” changes). We seek to characterize these changes and develop new therapeutic strategies for those patients with ALK fusion-positive lung cancers whose tumors develop this type of resistance.