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Table 2 Potential factors that may cause resistance to trastuzumab emtansine

From: Trastuzumab emtansine: mechanisms of action and drug resistance

Factors decreasing intracellular DM1 level  
  T-DM1 binding to HER2 Low cancer HER2 expression
HER2 down-regulation
Shedding of HER2 ectodomain
Masking of the trastuzumab binding epitope on HER2 p95HER2 expression
  Intracellular trafficking and lysosomal degradation Poor HER2-T-DM1complex internalization
HER2-T-DM1 recycling to plasma membrane
Failure of HER2 intracellular trafficking
Inefficient lysosomal degradation of T-DM1
  Drug efflux MDR1 expression
Other factors  
  Altered DM1 target Beta1-tubulin mutation
  Autocrine or stromal growth factors Overexpression of a beta3-tubulin isoform
  Modulators of the apoptotic pathway Microtubule-associated proteins
  Activation of cell survival pathways  
  1. HER2, human epidermal growth factor receptor-2; T-DM1, trastuzumab emtansine.