Table 5.

Factors affecting ErbB-targeted therapies for intrahepatic cholangiocarcinoma and other biliary tract cancers

Factors
Patient selection and sampling size
Suboptimal drug dosing and/or scheduling
Tumor microenvironment and bioavailability
Intratumoral heterogeneity in receptor expression and activation
Receptor dynamic effects
Mutational effects
Different mechanisms of acquired resistance
Constitutive overexpression of ErbB family ligands
Co-activation of multiple receptor tyrosine kinases resulting in signaling redundancy and interplay
Lack of uniform biomarkers to effectively predict therapeutic response
Co-morbid disease and toxicity