Irish scientists have established why some cancers are drug resistant, which has led to a novel chemotherapy treatment using lithium.
This breakthrough could improve outcomes for almost 4,000 people diagnosed in Ireland every year with oesophageal, gastric and colorectal cancers, which are responsible for almost 1,750 deaths.
The team based at University College Cork (UCC) and Cork University Hospital (CUH) found that adding lithium to the chemotherapy regime blocks cancer cells' ability to repair the internal damage normally inflicted by the treatment.
This makes chemotherapy more effective and reduces risk of the cancer returning again. Lithium has been used as “a mood stabiliser” in the treatment of neurological disorders but not in chemotherapy.
The research was funded by the charity Breakthrough Cancer Research and led by Dr Sharon McKenna. The findings were announced on Friday to coincide with World Cancer Day. In a clinical trial, which has enrolled its first few patients in Cork, the research team will be monitoring the safety of combining lithium with standard chemotherapy.
It will also investigate how well lithium works in combination with other drugs used to treat advanced forms of these cancers. Because this is an alternative use of a known drug (lithium), it is likely to have a shorter timeframe to be adopted for treatment – should it prove safe.
Colorectal cancer is the second most common cause of cancer-related death in Ireland – 1,010 deaths annually – with at least 2,819 new cases each year. Oesophageal and stomach cancers have two of the lowest five-year survival rates at 24 per cent and 30 per cent respectively.
Because these types of cancers are rarely detected early enough for surgery, as they are internal, chemotherapy is the most common treatment. However, the cancer cells can be highly resistant to chemo drugs, so cancers frequently come back.
The team identified that a cell recycling process called autophagy (self-eating) enabled the cells to repair themselves and recover but then found lithium blocks this ability to repair, which greatly enhances effectiveness of chemotherapy.
“We were so thrilled to find a combination that could potentially make an impact on the effectiveness of treatment and improve survival. We tested this new chemo-lithium combination in several pre-clinical models and found that tumours were being cleared much more effectively than single agent treatments,” said Dr O’Donovan, who made the key finding.
Consultant oncologist Prof Séamus O'Reilly, based at CUH and Mercy University Hospital, was so inspired by the results he undertook to lead the clinical trials.
He added: “The most difficult part of my job is seeing patients you think are going to respond well to treatment do badly. People whose lives should have been longer, whose cancer should have been cured, or whose suffering should have been less.”
More and more patients were being diagnosed with cancer in Ireland on a daily basis, so there is critical need to extend their lives, he said. “Patients don’t fail treatments but treatments sadly do fail patients. We urgently need treatment advances to cure more people and to help those that can’t be cured to live longer and better. That can only be found by investing in ground-breaking cancer research.”
“Many new cancer drug treatments are expensive, limiting their impact as societies and patients struggle to afford them. Lithium is much cheaper and could be globally accessible,” Prof O’Reilly noted.
Bowel cancer survivor Ger Stanton from Ballyvolane in Cork said the research sounded incredibly promising. "Cancer research helps so many people to live longer and better – and this announcement will bring so much hope to so many."
Breakthrough chief executive Orla Dolan said it was "a wonderful example of how patient-focused research supported by the generosity of the public can translate from the lab into new treatments in the clinic".
Over the past 20 years, Breakthrough has succeeded in bringing eight new treatments to clinical trial stage.
