2011 UALC
Magda Stumpfova, PhD
Dana-Farber Cancer Institute
Research Project:
Characterization of CRKL as a novel resistance mechanism to ALK inhibitors
Summary:
The ALK inhibitor crizotinib (Xalkori) has shown to be very effective in patients harboring ALK mutations, including the EML4-ALK fusion. However, as with other targeted therapies, patients become resistant to treatment. Dr. Stumpfova’s project will identify and characterize resistance mechanisms that develop to ALK tyrosine kinase inhibitors (TKIs), focusing on a new target, CRKL. She will study how CRKL leads to ALK TKI resistance, validate whether this resistance mechanism also occurs in NSCLC patients that have developed acquired resistance to crizotinib, and test strategies to overcome this resistance mechanism.
More Content:
Final Report
Dr. Stumpfova has linked CRKL to another known mechanism of resistance to ALK-targeted therapies, and is investigating further how these proteins interact to drive tumor growth to improve treatment strategies. Importantly, it appears that CRKL activation is of clinical significance, and may correlate with patient’s progression-free survival in patients with ALK+ lung cancers treated with ALK inhibitors. Studies are planned to assess CRKL’s potential as a prognostic biomarker.