RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer.
Olav EngebraatenChristina YauKristian BergElin BorgenØystein GarredMaria E B BerstadAne S V FremstedalAngela DeMicheleLaura van 't VeerLaura J EssermanAnette WeyergangPublished in: Nature communications (2021)
HER2 is a predictive biomarker for HER2-targeted therapeutics. For antibody-drug conjugates (ADCs; e.g., trastuzumab emtansine (T-DM1)), HER2 is utilized as a transport gate for cytotoxic agents into the cell. ADC biomarkers may therefore be more complex, also reflecting the intracellular drug transport. Here we report on a positive correlation between the early endosome marker RAB5A and T-DM1 sensitivity in five HER2-positive cell lines. Correlation between RAB5A expression and T-DM1 sensitivity is confirmed in breast cancer patients treated with trastuzumab emtansine/pertuzumab in the I-SPY2 trial (NCT01042379), but not in the trastuzumab/paclitaxel control arm. The clinical correlation is further verified in patients from the KAMILLA trial (NCT01702571). In conclusion, our results suggest RAB5A as a predictive biomarker for T-DM1 response and outline proteins involved in endocytic trafficking as predictive biomarkers for ADCs.
Keyphrases
- metastatic breast cancer
- epidermal growth factor receptor
- poor prognosis
- end stage renal disease
- study protocol
- clinical trial
- ejection fraction
- positive breast cancer
- glycemic control
- newly diagnosed
- phase ii
- chronic kidney disease
- randomized controlled trial
- peritoneal dialysis
- stem cells
- binding protein
- tyrosine kinase
- magnetic resonance imaging
- skeletal muscle
- metabolic syndrome
- drug delivery
- young adults
- reactive oxygen species
- childhood cancer
- drug induced