According to Cancer Research UK, one in two people in the UK will be diagnosed with cancer at some point in their lives – quite a scary statistic, isn’t it? With the number of cases increasing each year, it is hardly surprising that even more money is being invested into research to contribute to finding a ‘cure’ for cancer.
Cancer is a condition that is defined as the uncontrolled division of abnormal cells. Clusters of these cells can form tumours, which are described as benign when they stay within the region of origin, and malignant cancer can occur when the abnormal cells undergo metastasis (when cells detach from the tumour and spread to other parts of the body via the bloodstream).
It is unlikely that we will ever find cancer’s ‘Magic Bullet’ – a one-size-fits-all cure – but current treatments which are potentially effective include Surgery, Radiotherapy (using ionising radiation to control or kill malignant cells), Chemotherapy (treatment with anti-cancer drugs) and Immunotherapy (using the immune system to target the cancer cells). The above treatments aim to remove or destroy the abnormal cells that cause cancer, but this blog post is about another form of cancer treatment that is in development… Instead of killing the cancerous cells, why don’t we send them to sleep?
The study that was published in Nature earlier this month found that shutting down the activity of the KATA6 proteins does not destroy the cancerous cells, but instead halts any further cell division (senescence), hence preventing the tumour from developing and malignancy occurring.
KAT6A and KAT6B are involved in embryonic development (when we are ‘made’ in the womb), but can also contribute to the induction of cancer. It has been shown in a previous study that reducing the expression of KAT6A quadrupled the life expectancy of animal models with lymphoma (a cancer of the white blood cells). The aim of this more recent study was to investigate whether blocking the activity of the KAT6 proteins could treat cancer patients.
To block the activity of the KAT6 proteins, Dr Tim Thomas and Dr Anne Voss of the Walter and Eliza Hall Institute, Melbourne, needed to decide on a target protein which could inhibit the action of KAT6A and KATB from a library of half a million compounds. After deciding on the molecule WM-8014, which binds to mammalian blood plasma protein and blocks it activity, they showed that this molecule could also cause the senescence of Zebrafish* cells with cancer. The molecule was further modified for the potential to work in mammals, and the newly-adapted WM-1119 molecule was subsequently capable of eliminating lymphomas in mice.
There were questions associated with this treatment that were addressed by Thomas;
What about the ‘sleeping’ cells left in the body? – “The body will eventually recognise them as abnormal and clear the cells.”
Will blocking proteins interfere with normal function? – It was mentioned that KAT6A appears unnecessary in adults, who would be the main cohort receiving the protein-blocking treatment.
By making cancer cells dormant, this avoids the problems associated with invasive treatments. A treatment that kills cancer cells also runs the risk of killing healthy cells, which could lead to tissue damage. Radiation treatments may mutate healthy cells as well and cause further abnormal cell division. Additionally, blocking the activity of the KAT6 proteins is also expected to work against many different cancer types in a wide range of organs, and genomics (looking at the genome) would allow patients who are likely to respond well to the treatment to be identified easily.
For now, more work needs to be done on the molecule as high doses were required to eliminate the cancer in mice, and it was uncertain whether the effect of inhibition of the KAT6 proteins was permanent. Further testing of safety and efficacy would be required before WM-1119 could be administered in trials with cancer patients, although the risk of long-lasting side effects appears to be low.
*Zebrafish is a common model organism used in research because they are genetically similar to humans and their embryos can develop outside of the mother’s body.