Cancer Research

Cancer Research UK is urging a solution to the impasse over the advanced prostate cancer drug abiraterone, which has been turned down by NICE.

Physical activity, when appropriate, can improve patients' health and quality of life after they finish treatment, according to large analysis of over 30 studies of exercise and cancer, published in the BMJ.

A test being introduced by the Government is effective at detecting bowel cancer, a US study has confirmed.

Many critical cell functions depend on a class of molecules called purines, which form half of the building blocks of DNA and RNA, and are a major component of the chemicals that store a cell’s energy. Cells keep tight control over their purine supply, and any disruption of that pool can have serious consequences.

In a new study, MIT biological engineers have precisely measured the effects of errors in systems for purine production and breakdown. They found that defects in enzymes that control these processes can severely alter a cell’s DNA sequences, which may explain why people who carry certain genetic variants of purine metabolic enzymes have a higher risk for some types of cancer.

DNA usually consists of a sequence of four building blocks, or nucleotides: adenine, guanine, cytosine and thymine (the A, G, C and T “letters” that make up the genetic code). Guanine and adenine are purines, and each has a close structural relative that can take its place in DNA or RNA. When these nucleotides, known as xanthine and hypoxanthine, are mistakenly inserted into DNA, they cause mutations. They can also interfere with the function of messenger RNA (mRNA), which carries DNA’s instructions to the rest of the cell, and the RNA molecules that translate mRNA into proteins.

“A cell needs to control the concentrations very carefully so that it has just the right amount of building blocks when it’s synthesizing DNA. If the cell has an imbalance in the concentrations of those nucleotides, it’s going to make a mistake,” says Peter Dedon, a professor of biological engineering at MIT and senior author of the study, which is appearing in the Proceedings of the National Academy of Sciences the week of Jan. 30.

In addition to forming the backbone of DNA and RNA, purines are also a major component of ATP, the cell’s energy currency; other molecules that manage a cell’s energy flow; and small chemical cofactors required for the activity of thousands of cell enzymes.

Abnormal metabolism

Dozens of enzymes are involved in purine metabolism, and it has long been known that malfunction of those enzymes can have adverse effects. For example, losing a purine salvage enzyme, which recovers purine nucleotides from degraded DNA and RNA, leads to high blood levels of uric acid, causing gout and kidney stones — and in extreme cases, a neurological disorder called Lesch-Nyhan syndrome. Losing another salvage enzyme produces a disease called severe combined immunodeficiency.

Abnormal purine metabolism can also lead to side effects for people taking a class of drugs called thiopurines. In some people, these drugs, often used to treat leukemia, lymphoma, Crohn’s disease, rheumatoid arthritis and organ-transplant rejection, can be metabolized into toxic compounds. Genetic testing can reveal which patients should avoid thiopurine drugs.

In the new study, Dedon and his colleagues disrupted about half a dozen purine metabolism enzymes in E. coli and yeast. After altering the enzymes, the researchers measured how much xanthine and hypoxanthine was integrated into the cells’ DNA and RNA, using a highly sensitive mass spectrometry technique they had previously developed to study DNA and RNA damage caused by inflammation.

They found that the malfunctioning enzymes could produce dramatic increases — up to 1,000-fold — in the amounts of hypoxanthine incorporated into DNA and RNA in place of adenine. However, they saw very little change in the amount of xanthine inserted in place of guanine. 

Chris Mathews, a professor emeritus of biochemistry and biophysics at Oregon State University, says the finding could help researchers better understand how defects in purine metabolism produce disease. “This paper opens the door to numerous studies — for example, looking into the biological effects resulting from the accumulation of abnormal bases in DNA and RNA,” says Mathews, who was not involved in this study.

Scientists have found quite a bit of genetic variation in purine metabolic enzymes in humans, so the research team plans to investigate the impact of those human variants on xanthine and hypoxanthine insertion into DNA. They are also interested in studying the metabolism of the other two nucleotides found in DNA, cytosine and thymine, which are pyrimidines.

New studies have found genes linked to two types of aggressive childhood brain tumour, and could aid the development of effective treatments.

The Government has today launched a new campaign to help people spot the warning signs of bowel cancer.

Researchers in the US have developed a gene test that seems to be able to predict which early stage (stage I) non-small cell lung cancer patients have the poorest prognosis.

Cancer Research UK's Drug Development Office has opened the first trial of a new type of drug to treat children aged from six months to 18 years with acute leukaemia, who are no longer responding to treatment.

Research in the US has found that oral infection with the human papillomavirus (HPV) may be more common among men than women.

Cancer Research Technology, the commercial arm of Cancer Research UK, has today launched Acublate Limited, a spin-out company which will develop a next-generation High Intensity Focused Ultrasound (HIFU) surgery device to treat a range of solid tumour types.

Ovarian cancer patients who carry BRCA1 or BRCA2 mutations are significantly more likely to survive the disease than women without these faulty genes, according to research published in the Journal of the American Medical Association.

Dutasteride, a drug already used to treat men with enlarged prostates, can also slow the growth of early-stage prostate cancer that hasn't spread, according to research from Canada.

Cancer Research UK scientists have created the first 3D structure of a key protein that protects against the development of cancer, according to research published in Nature Structural & Molecular Biology today.

Scientists have discovered the gene behind a rare skin condition that predisposes to oesophageal cancer, according to a study part-funded by Cancer Research UK.

As the post-Christmas January blues take hold, young people are risking damage to their health and appearance by using sunbeds on the recommendation of friends and family, according to a new survey by Cancer Research UK.

An international study has uncovered how secondary skin cancers sometimes develop in malignant melanoma patients who are treated with an experimental drug.

Laboratory research in the US has discovered that a little-studied 'gatekeeper' cell may prevent cancer spreading around the body.

The authors of a study showing that hormone replacement therapy (HRT) increases the risk of breast cancer have defended their findings, following criticism from a team of experts linked to pharmaceutical companies that make the treatment.

A fluorescent dye that can be sprayed onto the oesophagus - the food pipe - could be used to detect oesophageal cancer earlier and spare patients unnecessary treatment, according to research published today in Nature Medicine.

Eating too much processed meat may increases the risk of pancreatic cancer, new research published in the British Journal of Cancer finds today.