The antibody-drug conjugate trastuzumab emtansine (T-DM1; Kadcyla) extends the survival of HER2-positive metastatic breast cancer patients. However, both acquired and intrinsic resistance limit its effectiveness and there are no reliable biomarkers for predicting the tumour response to T-DM1. Applying advanced genetic methods, we have identified a panel of 612 genes that we hypothesise to be involved in T-DM1 resistance. Here, we propose to validate the pre-selected candidate genes to select those with the highest potential to modify T-DM1 activity. We will apply cellular and animal models to check how inactivation of these genes influences the response to T-DM1. Finally, we will correlate their activity with the oncologic response of breast cancer patients to T-DM1 therapy. In the long term, our work could be applied to identify breast cancer patients most likely to benefit from T-DM1 or those patients who are most likely to develop resistance.

FIRST NAMED INVESTIGATOR: Dr Barbara Lipert
HOST INVESTIGATOR: The University of Auckland