Dr Tan Nguyen
The Walter and Eliza Hall Institute of Medical Research
Bowel and lung
What is the project?
Autophagy is a natural process by which the cells of our body destroy, recycle and re-use unnecessary or damaged components. This process occurs within specialised structures called ‘lysosomes’ and is required by all living cells in order to remain healthy. However, autophagy can also be hijacked by cancer cells to help them grow and in recent years, drugs targeting lysosome function or autophagy have been developed to prevent tumour development. Recently, a new form autophagy has been described known as RNAutophagy whereby cells degrade their own RNA, a form of genetic material similar to DNA. This process was reported to require an RNA transporter called SIDT2 which channels RNA into the lysosome for destruction. During my PhD, I discovered that loss of SIDT2 is slows down cell growth and that mice lacking SIDT2 developed smaller tumours and survived longer compared to controls. This shows for the first time that SIDT2 is required for tumours to grow and suggests that RNAutophagy can be therapeutically targeted in patients with cancer. Continuing from my PhD work, I now aim to further understand how SIDT2 is involved in tumour development and to determine whether inhibition of SIDT2 can be used to further sensitise cancer cells to current chemotherapeutic drugs.
What is the need?
While there is strong evidence and rationale for the development and use of inhibitors of autophagy in the treatment of human cancers, non-specific inhibition of this key cellular pathway can lead to significant adverse effects. Therefore, more specific targeting of the autophagy pathway may provide a useful strategy for cancer therapeutics.
What are you trying to achieve?
This study could provide the basis and justification for the development and use of drugs that specifically inhibit SIDT2 activity. Such inhibitors may lead to improved therapeutic outcomes for cancer patients, and will provide further progress towards the ultimate goal of cancer eradication.
Cancer Council Postdoctoral Fellowship