Studying tumour evolution and immune cell composition in uterine leiomyosarcoma to define novel effective combinations of targeted therapies

• PhD

Uterine leiomyosarcoma (uLMS) is a rare malignancy that is considered extremely aggressive and difficult to treat. Standard treatments involve surgery and chemotherapy but metastatic relapse is common and invariably fatal (Arend, Oncol 218 23:1533). We, and others, have recently discovered at least 10% of individuals with uLMS may respond to inhibitors of poly (ADP-ribose) polymerase (PARP) (Dall, J Exp Clin Can Res 2023 42(1):112). Unfortunately, resistance to PARP inhibitors (PARPi) will eventually arise.

In this project, novel targets for therapeutic intervention will be identified by studying gene expression (in single cells with spatial information) and immune cell composition at different stages before and after therapy. Urgent research efforts are needed to develop effective combination therapeutic strategies that improve survival outcomes for individuals with uLMS.

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 92 have been diagnosed with uLMS. 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.