HO-1 drives autophagy as a mechanism of resistance against HER2-targeted therapies.

Purpose: Targeted therapies have resulted in major advances in the treatment of HER2-positive breast cancers. Despite this, up to 70% of patients will develop resistance to treatment within 2 years and new strategies for targeting resistant disease are needed.

Methods: To identify potential resistance mechanisms, we used the mouse MMTV-NIC-PTEN spontaneous model of HER2-positive breast cancer and the pan-HER family kinase inhibitor sapatinib.

Mouse models of metastasis: progress and prospects.

Metastasis is the spread of cancer cells from a primary tumor to distant sites within the body to establish secondary tumors. Although this is an inefficient process, the consequences are devastating as metastatic disease accounts for >90% of cancer-related deaths. The formation of metastases is the result of a series of events that allow cancer cells to escape from the primary site, survive in the lymphatic system or blood vessels, extravasate and grow at distant sites.

Use of a genetically engineered mouse model as a preclinical tool for HER2 breast cancer.

Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapies presents a major clinical problem. Although preclinical studies have identified a number of possible mechanisms, clinical validation has been difficult. This is most likely to reflect the reliance on cell-line models that do not recapitulate the complexity and heterogeneity seen in human tumours.