Fig. 2: ERBB2 point mutations confer sensitivity to irreversible ErbB inhibitors.

Ex vivo inhibitor profiles for patients 08-00053 (ERBB2^R188C), 09-00076 (ERBB2^P489L), and 13-00319 (ERBB2^L1157R) with the IC₅₀ measure of response to each reversible (a; erlotinib, gefitinib, and lapatinib) and irreversible (b; pelitinib and canertinib) inhibitor shown on the Y axis. Sensitivity is determined by % median IC₅₀, which has historically been a marker for patient samples remarkably sensitive to a screened inhibitor [10]. Solid black lines indicates 20% of median IC₅₀ for the overall cohort while the gray dotted line indicates 20% of the median IC₅₀ for samples with similar diagnoses (i.e., acute myeloid leukemia or acute lymphoid leukemia). c ERBB2-mutant-transformed Ba/F3 cells are sensitive to irreversible inhibitors. Five replicates of WT and mutant ERBB2 Ba/F3 cells were plated with varying concentrations of afatinib, neratinib, and poziotinib for 72 h. ERBB2^WT cells were plated in media supplemented with IL-3. Cell viability was determined using a tetrazolamine-based viability assay. Viability is represented as a percentage of the untreated control. The average mean ± SEM is shown.