Screening of genetically identified compounds for endometrial cancer therapy

Can be adapted in scope for Honours or PhD.

BACKGROUND

There is promising evidence that genetic studies of cancer will advance the development of new therapies. For example, clinically approved drugs are more likely to target proteins that have been linked to disease traits through genome-wide association studies (GWAS) than proteins with no such links. Indeed, several drugs already used to treat endometrial cancer are known to target proteins that have been linked to genetic variation associated with endometrial cancer risk. To discover genes regulated by endometrial cancer GWAS variants, and hence potential drug targets, we have performed functional genomic analyses of endometrial cancer. These analyses revealed candidate targets tractable to small molecule inhibition. Three of these candidates are now undergoing a virtual small molecule screen, using artificial intelligence to prioritise compounds. Additionally, we have performed bioinformatic analysis of GWAS data, revealing existing drugs that may have efficacy for endometrial cancer.

AIM

To screen compounds, selected by artificial intelligence, for activity against candidate protein targets identified from endometrial cancer GWAS and assess the anticancer effects of prioritised compounds and existing drugs for anti-cancer effects.

APPROACH

We will use commercially available and previously reported assays to screen for the effects of compounds on the activity of candidate protein targets. Compounds with the strongest effects in protein assays will be prioritised for assessment of anti-cancer effects in novel endometrial organoid models. Existing drugs identified through bioinformatic analysis will also be tested in organoid models.

OUTCOME

Identification of novel compounds or existing drugs that have anti-cancer effects in organoid models would provide the necessary evidence for further development of these molecules, with the ultimate aim of conducting clinical studies of endometrial cancer.