Identifying effective combination therapies including HER2-targeting agents for the treatment of aggressive endometrial cancers

• Honours

High-grade serous endometrial carcinoma (HGSEC) is the most aggressive form of endometrial cancer, with a high mortality (Amant, Lancet 2005 366(9484):491). Approximately 30% of HGSEC express high levels of the human epidermal growth factor receptor 2 (HER2) (Fader, Clin Can Res 2020 26(15):3928). Unlike the great success in treating HER2-positive breast cancers, HER2 inhibitor therapies (HER2i) have not been as effective for treating HER2-positive HGSEC (Fader, Clin Can Res 2020 26(15):3928).

This project involves carrying out a drug screen utilising HER2-positive HGSEC cell lines to identify effective HER2i-based combination therapies. The most effective combination therapies will be validated in our HER2-positive organoid models, with functional behaviour monitored by live-cell imaging. This study will guide future therapeutic strategies that are desperately needed for this aggressive cancer.

The Scott Laboratory, in the Cancer Biology and Stem Cells Division at WEHI, is investigating novel treatment strategies in ovarian and rare cancers. About 900 patients with rare cancers have so far been consented to the Stafford Fox Rare Cancer Program in the Scott lab, of which 68 have been diagnosed with HGSEC. We study the molecular features of these rare tumours and develop a range of preclinical models, including cell lines, organoids and mouse models. These preclinical models can then be used to study the rare cancers in more detail and test combinations of therapies to hopefully identify more effective treatment options.