Each year, over 40,000 people in the UK are diagnosed with colorectal cancer. Affecting 1 in 15 men and 1 in 18 women during their lifetimes, according to the charity Bowel Cancer UK, it’s the fourth most common form of cancer in Britain – and the second biggest killer. But a drugs trial carried out in the US may offer new hope in treating the disease.
Colorectal cancers can take many forms, but around 5 to 10 per cent of them can be characterised as ‘mismatch repair-deficient’ (MMrD). This means there have been mutations in genes that are involved in ensuring the successful duplication of other genes, with the result that MMrD cells tend to feature many genetic mutations, which can lead to cancer.
What’s more, if cancer does arise, MMrD tumours tend to be less responsive to chemotherapy and radiation treatments than other forms – leaving invasive surgery as the only option for patients afflicted by this type of tumour. In recent years, however, there has been some significant progress in the use of immunotherapy drugs to treat various types of MMrD tumour in different parts of the body.
The specific drugs involved are called PD-1 blockers, and work by inhibiting the activity of protein called PD-1 that is found on the surface of the body’s T-cells – the white blood cells that are responsible for fighting antigens. Normally, PD-1 and another protein called PD-L1 prevent T-cells from attacking cancer cells, but restricting PD-1 cells’ activity leaves the T-cells free to fight the tumour.
Now, a team of researchers at the Memorial Sloan Kettering Cancer Center in New York used a PD-1 blocking drug called dostarlimab to treat 14 patients with MMrD stage two or stage three rectal cancers. The patients were given a dose of the drug every three weeks for six months, with a view to continuing treatment with chemoradiation and surgery afterwards, if required.
The researchers found, however, that no such further treatment was required – and up to two years down the line, all 14 patients are still completely tumour-free. This offers hope that dostarlimab (or similar drugs) could help to vastly reduce the number of colorectal cancer patients that require surgery each year.
“Surgery and radiation have permanent effects on fertility, sexual health, bowel, and bladder function. The implications for quality of life are substantial, especially in those where standard treatment would impact childbearing potential,” said Dr Andrea Cercek, who co-led the research alongside her MSK colleague Dr Luis Diaz, Jr. “As the incidence of rectal cancer is rising in young adults, this approach can have a major impact.”
Writing in the New England Journal Of Medicine, another cancer researcher – Dr Hanna K Sanoff from the UNC Lineberger Comprehensive Cancer Center – welcomed the findings, saying that they were “very encouraging”, but also pointing out that they “need to be viewed with caution until the results can be replicated in a larger and more diverse population”.
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