Breakthrough that opens up new treatment possibilities for blood cancer

29th November 2023

Worldwide Cancer Research scientist Dr Vincenzo Giambra, and his team in Italy, have found new evidence that cancer cells are regulated by ‘clockwork’ genes. They hope that targeting these genes might one day lead to new ways to cure T-cell acute lymphoblastic leukaemia - a type of blood cancer that can be particularly difficult to treat.

What is our circadian rhythm?

Nearly all living creatures have a circadian rhythm - the regular pulsing changes that happen over every 24-hour cycle, usually in response to light and dark. This internal rhythm regulates how we live- it’s why we feel hungry at certain times, or why we feel jet-lagged and ‘out-of-sync’ when we travel to a different time zone.

Our circadian rhythm is also important for our health- some studies have linked long-term disruption in our circadian rhythm with an increased risk of developing certain health conditions, including some types of cancer

But how do our cells know what time of day it is? With the help of a fully working molecular ‘clock’ - a complex set of genes that ‘tick’ in precise time to signals from our brain, and help to regulate daily cell activity. 

Even cancer cells have these tiny molecular clocks. And intriguingly, some cancer cells appear to be heavily regulated by them- even when healthy cells are not. Some researchers now believe that these molecular clocks might even represent a brand-new target for new cancer drugs. 

Searching for a new way to treat T-cell acute lymphoblastic leukaemia (T-ALL)

This is where Dr Vincenzo Giambra comes in. Dr Giambra is interested in finding new ways to treat T-cell acute lymphoblastic leukaemia (T-ALL), a rare but aggressive type of blood cancer that develops from white blood cells. 

T-ALL affects both children and adults, and can progress quickly if not treated. The usual treatment is chemotherapy, sometimes with radiotherapy and stem cell therapy, and in children, about 4 out of 5 cases can be successfully treated. But just 2 out of 5 adult cases of T-ALL are treated successfully, and unfortunately, the cancer can often come back. 

New treatments are desperately needed, and thanks to our Curestarters, we were able to give Dr Giambra vital funding to investigate new ways to target this cancer. 

What did the researchers find?

‘Clockwork’ genes are already known to help regulate some types of blood cancer cells, so first Dr Giambra and his team wanted to find out how important these genes are for T-ALL cells. 

Using cells grown in the lab, the researchers blocked two important clockwork genes, called BMAL1 and CLOCK, from working. 

They found that not only does this type of leukaemia cell have fully intact and working molecular clocks, but more importantly, stopping these clocks reduced the ability of the cancer cells to grow. 

Next the researchers used mice with a form of human T-ALL to investigate whether levels of BMAL1 and CLOCK also regulated the activity of a type of hard to treat ‘beginner’ cancer cell, called a ‘leukaemia initiating cell’. 

These cells are a bit different to ‘normal’ cancer cells because they are thought to be the very first cancer cells that develop. They are hardy, and much trickier to completely eradicate with treatment. 

They also have the potential to regenerate, meaning that if treatment does not completely clear these cells, they can start to regrow into a new cancer. These cells are thought to be one major reason why some types of leukaemia come back after treatment. 

Importantly, the researchers gathered good evidence suggesting that these clock genes are also important for leukaemia initiating cells. They found that in these mice, cancer cells that had reduced levels of molecular clock activity also had reduced numbers of leukaemia initiating cells, suggesting a link between the two. 

What does this mean for patients with blood cancer? 

This is an early, but important finding. It is only the start, but this new work could potentially help to pave the way to new treatments for T-ALL, and also be the first step towards finding new ways of detecting aggressive forms of the disease in patients. Screening patients for these ‘red flags’ might one day help to make sure that patients can receive the most effective treatment, as soon as possible.

Dr Giambra said of the discovery:

“Put simply, we have found that T-ALL cells have intact circadian clock mechanisms, and that the correct ticking of this clock is needed to keep the cells growing,” 

“We need much more research to make sure, but our work suggests that it could be worth investigating if disrupting the clockwork machinery could potentially be an effective way to target and treat the cancer. It also opens the way for more studies to investigate if clockwork genes like BMAL1 and CLOCK could be used to detect especially aggressive cases of leukaemia in patients."

Vincenzo Giambra Dr Vincenzo Giambra, Worldwide Cancer Research scientist
We are so grateful to all Worldwide Cancer Research supporters, for helping to make this work possible.

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