RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34741021.
- Also identified by DOI 10.1038/s41467-021-26018-z and PMC identifier 8571323.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Ado-Trastuzumab Emtansine
- Antibodies, Monoclonal, Humanized
- Biomarkers, Tumor
- Breast Neoplasms
- Trastuzumab
- rab5 GTP-Binding Proteins