Scientists identify tumours that are more likely to become resistant to cancer drugs

CANCER RESEARCH UK scientists have made an important step towards developing personalised bowelA common name for the large and/or small intestines. cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. treatment by identifying which tumours are more likely to become drug resistantA microbe, such as a type of bacteria, that is able to resist the effects of antibiotics or other drugs., according to research published in Cancer Research today. The team at Cancer Research UK’s London Research Institute treated two classes of bowel cancer cells grown in the laboratory with around 250 compounds. These included common chemotherapyThe use of chemical substances to treat disease, particularly cancer. drugs used in bowel cancer and newer ‘targeted’ drugs which block specific faults in cancer cells. 

Cells in one group had a stable set of 46 chromosomes.  The cells in the other group were chromosomally unstable bowel cancer cells produced when faults occurred whilst the cells were dividing. 

The team found that chromosomally unstable bowel cancer cells are significantly more resistant to a large number of chemotherapy treatments and targeted drugs, than cells with a stable chromosome number. And tumours with stable chromosomes are more likely to respond to drugs. These results mean that determining the chromosomal status of tumours may provide useful information on whether bowel cancer patients will benefit from certain treatments. Chromosomally unstable tumours are the most aggressive, accounting for 70 per cent of all bowel cancer cases. 

Lead author of the report, Dr Charles Swanton, said: “One of the most important questions in cancer medicine is to find out why drugs work better in some patients than others – so doctors can prescribe the most beneficial treatments. “

Dr Lesley Walker, Cancer Research UK’s Director of Cancer Information, said: “We’re making excellent progress in the treatment of bowel cancer. People diagnosed today are twice as likely to survive for at least ten years than those diagnosed in the 1970s and our work has played a significant part in this progress.”  

“Developing treatments according to the geneticRelating to the genes, the basic units of genetic material. profile of patients is the next big focus - as not all bowel cancers are the same. These findings will help us unravel the underlying disease causes to tailor treatment to different groups of patients and find better drugs for advanced disease. The next stage will be to confirm this early research with larger studies.”

"This is extraordinary work towards the creation of 'designer chemotherapy agents' for patients with colorectal cancer. 

The concept is simple - can we predict from the characteristics of cancer cells which patients are likely to benefit from chemotherapy. Furthermore, by  understanding why some of these cells are resistant to treatment, could lead to the development of newer agents that can destroy them.  

The above work by Dr Swanton and colleagues suggests that unstable chromosomes in the genetic make-up of the cancer cells may explain why some patients do badly. Arguably, this finding may represent a watershed in future attempts to tailor chemotherapy to each patient suffering from bowel cancer. However, a larger trial is necessary to confirm these preliminary findings before possible clinical application."

UK colorectal cancer expert, Mr Austin Obichere

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