Researchers have broken the code of an enzyme that plays a key role in the growth of most cancers, opening a path that potentially leads to a new class of anti-cancer drugs, according to a study released Sunday. The study is hailed as a breakthrough in fundamental cancer biology, but much work remains before the finding may be translated into next-generation therapies. The enzyme, called telomerase, “is an ideal target for chemotherapy because it is active in almost all human cancer tumors, but inactive in most normal cells,” said Emmanuel Skordalakes, a professor at the Wistar Institute in Philadelphia who led the study. “That means that a drug that deactivates telomerase would likely work against all cancers, with few side effects.” In humans, telomerase adds short sequences of DNA known as telomeres to the ends of chromosomes, thus preventing damage and the loss of genetic information when cells divide. The enzyme is active mainly in cells that multiply frequently, such as embryonic stem cells, but is switched off in normal adult cells to avoid problems caused by runaway cell proliferation. In cancer cells, however, telomerase is activated, allowing the disease cells to replicate endlessly and achieve what scientists call “cellular immortality,” the hallmark of all cancers. This is the first time a complete view of a critically important protein within the telomerase molecule is provided. They have found how, at an atomic level, the enzyme replicates the tips of chromosomes, a process critical to the development of tumors. The breakdown of this same mechanism is also involved in the aging process, which means any new inhibitor drugs might also help boost longevity. Meanwhile, three different studies published by the journals Nature Genetics and Nature Medicine, uncovered genetic flaws that separately boost the risk of a common form of leukaemia and bowel disease in children and may also influence obesity and fertility. A team led by Richard Houlston of Britain's Institute of Cancer Research found six genetic variants that increase vulnerability to chronic lymphocytic leukaemia (CLL), which accounts for roughly a quarter of all leukaemia cases. The variants occur in genes that play a role in the proliferation of so-called B cells, a type of white blood produced in the bone marrow. Individually, these variants each contribute to a modest increase in the risk of CLL, but a person with all six faces an eight-fold increase. In the United States, scientists led by researcher Marc Montminy of the Clayton Foundation Laboratories for Peptide Biology found that a gene switched on by leptin – a hormone that tells the brain when the body has sufficient nutrition – is involved in appetite disorder and infertility. The discovery was found in the brain of mice, but there are likely to be strong similarities in humans. Variations of the gene, called TORC1, could play a part in obesity and infertility, as they could send the wrong signals to the brain as to whether food is needed and whether the body has sufficient energy stores for reproduction. A third study, entailing a trawl through the genetic code of thousands of people, netted two new genes involved in childhood inflammatory bowel disease (IBD), a painful condition that includes Crohn's disease and ulcerative colitis.
