Nom Nom Nom Autophagy!

If you’re anything like me then you will be fascinated by autophagy.  It’s a process that cells go through to deal with starvation.  Much in the same way that humans as an organism would die without food, cells too, suffer the same fate unless they are kept happy with a constant supply of nutrients.  If we are hungry we eat.  If a cell is starved of glucose it doesn’t have the option of grabbing a Mars bar so instead has developed an intricate survival mechanism - Autophagy.

This process literally means ‘to self eat’ and in short involves break down of the less important components of the cell into the building blocks required to keep the cell alive.  Importantly this will include amino acids - the base unit of a protein - which allows synthesis of new proteins and cell survival.  As a survival mechanism it is not surprising that autophagy is linked to cancer.  What is more surprising (or perhaps not when you compare it to other processes linked to cancer) is that there is sufficient evidence to say that autophagy may be oncogenic (cause cancer) or tumour suppressive (prevent cancer) depending on many other interacting factors.  The link between autophagy and cell fate is currently a hot research topic and as our understanding of it improves it may become clear that autophagy can be used as a therapeutic target to tackle cancer.

Confocal image of MCF-7 (human breast cancer cells) treated with the chemotherapeutic agent etoposide.  Stained with acridine orange the green shows where the dye has stained the nucleus and the red is where the cell is starting to 'digest' parts of itself in small capsules called autophagasomes.  (courtesy of me and Aston University)

I have been involved in breast cancer research for the past 4 years.  Treatment for the most common types of breast cancer have been very successful and helped to not only extend lives but also ‘cure’ breast cancer sufferers.  A major issue currently facing cancer researchers is the development of resistance to chemotherapy regimes that can result in a tumour growing back or treatments becoming ineffective in certain patients.  It is not fully understood how this occurs but a variety of genetic and epigenetic changes have been attributed to the evolution of tumours carrying drug resistance cells.  Darwinian theory would naturally select for these resistance cells following the selective pressure of an anti-cancer therapy and could give rise to a resistant tumour.  This phenomenon is fascinating and I would recommend reading more about it to any reader who has an underling interest in cancer biology.

So how does this all link to autophagy? Well quite simply, Autophagy has been shown to be a direct cause of drug resistance in cancer cells.  By helping the cell to survive under times of extreme stress, such as being bombarded with a nasty chemotherapeutic agent, the probability of survival-elite clones taking over a tumour population is increased dramatically.  Recent research proposes autophagy inhibitors may be a way to reverse or impair drug resistance in cancer but because of the complex cellular network controlling autophagy, it is not yet known how effective they may be clinically.  This is a major area of current cancer research and expect some exciting breakthroughs to take place soon.