Using CRISPR-Cas9 to predict sensitivity to trastuzumab emtansine

Over 3000 diagnoses and 600 deaths are attributable to breast cancer in New Zealand each year. One-quarter of breast cancers is driven by increased amounts of a gene called HER2, which can be targeted with the drug trastuzumab (Herceptin). Trastuzumab markedly improves outcomes for HER2-positive breast cancer; unfortunately, treatment resistance develops in many patients, leading to poor prognosis. A new drug, trastuzumab emtansine (T-DM1 or Kadcyla), was recently approved for treating HER2-positive, metastatic breast cancer that has failed prior treatment with trastuzumab. However, T-DM1 shrinks tumours in only half of patients and the reasons why others are resistant remain unclear. This research uses a cutting-edge genetic tool –CRISPR-Cas9 – to identify genes that control (and thus predict) the sensitivity and resistance to T-DM1 in breast cancer. We aim to reduce the distressing uncertainty associated with treating this illness and to enable patients and their caregivers to make informed treatment decisions.

HOST INVESTIGATOR: University of Auckland