Study 4: Response of a PIK3CA-mutated cell line, insensitive to a PIK3CA inhibitor, to a pan-PI3K inhibitor

  • A PI3KCA-mutated cell line, HCC1954, was studied to compare PI3K signaling activity measured by the CELsignia Test and tumor growth inhibition in a xenograft mouse model.  
  • The CELsignia test found that signaling activity associated with the PI3K-α isoform was normal, despite the presence of PIK3CA mutations.  However, the CELsignia Test found that pan-PI3K signaling activity was abnormal.   
  • The CELsignia signaling results were compared to xenograft study results that evaluated a PI3K-α inhibitor (alpelisib) and a pan-PI3K inhibitor (taselisib). 
    • A third-party study reported that alpelisib, a PI3K-α inhibitor, had no anti-tumor effect on an HCC1954 xenograft model.  
    • Celcuity studied a HCC1954 xenograft mouse model using a pan-PI3K inhibitor (taselisib).  The Celcuity study found that taselisib induces a significant anti-tumor effect in the HCC1954 tumor (79%).
  • PI3K signaling activity measured by the CELsignia Test directly correlated to tumor growth rate inhibition in contrast to the PIK3CA molecular test, which showed no correlation.  

Pathway Activity AssessedCELsignia ScoreAnti-tumor effect of matching drug
PI3K-a signalingNormalNo reduction (alpelisib)
Pan-PI3K signalingAbnormal79% reduction (taselisib)