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RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer

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Listed:
  • Olav Engebraaten

    (Oslo University Hospital
    Oslo University Hospital
    University of Oslo)

  • Christina Yau

    (University of California San Francisco)

  • Kristian Berg

    (Oslo University Hospital
    University of Oslo)

  • Elin Borgen

    (Oslo University Hospital)

  • Øystein Garred

    (Oslo University Hospital)

  • Maria E. B. Berstad

    (Oslo University Hospital)

  • Ane S. V. Fremstedal

    (Oslo University Hospital)

  • Angela DeMichele

    (University of Pennsylvania)

  • Laura van ’t Veer

    (University of California San Francisco)

  • Laura Esserman

    (University of California San Francisco)

  • Anette Weyergang

    (Oslo University Hospital)

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.

Suggested Citation

  • Olav Engebraaten & Christina Yau & Kristian Berg & Elin Borgen & Øystein Garred & Maria E. B. Berstad & Ane S. V. Fremstedal & Angela DeMichele & Laura van ’t Veer & Laura Esserman & Anette Weyergang, 2021. "RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26018-z
    DOI: 10.1038/s41467-021-26018-z
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