Uncontrolled cell growth is a consistent feature of cancer initiation and progression. Cell growth pathways are similar in vinegar flies and humans so our research has used the fly as a genetic model to find novel mechanisms controlling cell growth, which we will translate into mammalian cancer models to develop new treatments.
The focus of our work is the MYC protein, which is a potent driver of cell growth. Increased levels of this protein drives cells to overgrow, allowing cancer to get a foothold in the body.
Indeed, MYC is turned up way too high in at least 70% of all cancers. Our work using the vinegar fly has revealed key proteins required for controlling MYC, and we have demonstrated the same genes turn MYC on in they fly as in mince and humans.
What is the need?
Malignant glioma is the most common and deadliest brain tumour in adults, but there are currently no effective treatments and this diagnosis is a death sentence. Unlike many cancers (e.g. breast and prostate) there are no molecular prognostic markers to guide the treatement of gliomas. In fact, treatment decisions have changed very little in 30 years and outcomes vary significantly between glioma subgroups.
Glioma progression is strongly linked with increased abundance of the MYC-activator known as FUBP. Elevated FUBP correlates with poor patient survival, which suggests the FUBP-axis is a predictor for glioma aggression.
Our work has excellent potential for developing better biomarkers and improved targeting of glioma treatment.
What is the impact of this research?
Our work suggests that the FUBP protein is key to controlling levels of the MYC protein, and therefore cell growth. FUBP has been linked with a wide variety of cancers, including kidney, breast, liver, lung, bladder, prostate, gastrointestinal and brain.
To understand FUBP-related cancer, we need to know what growth signals activate FUBP to reduce MYC levels. Our studies have demonstrated the RAS and PI3K pathways activate MYC via FUBP1. This suggests FUBP1 will be essential for MYC-dependent brain tumour growth, and may provide a potential future drug target.
With drugs targeting RAS and PI3K pathways making their way to the clinic, understanding how to funnel these signals into FUBP activity, MYC expression and cancer progression is imperative to maximising drug efficacy. They will provide useful biomarkers for personalised chemotherapy, managing drug resistance, and ultimately informing new targets for future drug design.
These findings have enabled me to relocate to The ACRF Department of Cancer Biology and Therapeutics at The John Curtin School of Medical Research, ANU - an environment dedicated to rapidly translating our fundamental research to the clinic.
"Our work has excellent potential for developing better biomarkers and improved targeting of glioma treatment."