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Offbeat approaches to cancer research

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Offbeat approaches to cancer research
Cancer was responsible for an estimated 9.6 million deaths in 2018. Finding new ways to deal with this is an important endeavor. Scientists are progressing through various research methods; Here, five individuals share how they have built careers in cancer research while taking innovative approaches to the problem. Vera Gorbunova: Be open-minded Comparative biologist at the University of Rochester in New York. The naked mole rat (Heterocephalus glaber) is a remarkable creature in more ways than one. With its large, goofy incisors and waves of pale pink wrinkles, it’s unlikely to win any beauty pageants. But the naked mole rat has a few things going for it. It can live for more than 30 years. And it almost never gets cancer. When Vera Gorbunova set up her lab to investigate aging, she looked beyond the mouse and rat models typically deployed in the field. “Try to separate yourself from existing methods and think about the shortest path to the answer,” says Gorbunova. “If you want to understand how to avoid cancer, study animals that don’t have cancer. If you want to study aging, study animals that live longer.” Gorbunova and her colleagues cultured connective tissue cells from long-lived animal species. In a 2009 study 1, they noted that a process in natural anticancer protection called contact inhibition, which prevents cells from reaching a certain density, occurs at very low cell densities in nude mole rats. The researchers found that a thick fluid seen in mole-rat cell cultures was hyaluronan – a substance that has a wide range of functions in mammals, including tissue formation, wound repair and joint lubrication – and that the mole-rat K hyaluronan molecules weigh five times more. Degradation more slowly, compared to humans and mice 2. Both these differences slow the growth of precancerous cells and protect naked mole mice from cancer. Gorbunova’s group is now trying to mimic the cancer resistance of the mole rat and reproduce it in humans by identifying small molecules that inhibit the hyaluronan-degrading enzyme. Gorbunova acknowledges that it can be difficult for researchers to venture into unknown territory when they are just starting out in their careers. She suggests that early career scientists pursue one core project that is most likely to produce publishable results, and another that is more outside the box. She stresses the need to be open-minded. “When we started looking at naked mole rats, we didn’t really know what we were looking for. It’s important not to overlook unexpected results that don’t fit your hypothesis, because most of the time nature is smarter than us. it occurs. ” Bert van der Horst: Select positions carefully Chronobiologist at Erasmus Medical Center in Rotterdam, Netherlands. During his postdoc at the Erasmus Medical Center in Rotterdam, Netherlands, in the 1990s, Bert van der Horst studied Cockayne syndrome, a rare condition in which the skin is highly sensitive to DNA damage caused by ultraviolet light. He examined the subject more extensively. When they generated mice without two genes known to be important for repairing DNA damage directly caused by UV light, the genes did not have the DNA-repair function they had expected. Van der Horst later discovered that the genes – CRY1 and CRY2 – instead have essential roles in maintaining mammalian circadian rhythms. Van der Horst says, “I was fortunate that I had a supervisor who, even if he was skeptical, allowed me to explore my thoughts.” “I tell my students, ‘Keep your eyes open for the unexpected, and even if others think your idea is ridiculous, don’t give up’.” The publication of the gene’s discovery in 1999 was a turning point in van der Horst’s career, and he has since worked on chronology, and its relationship to disease. People whose circadian rhythms are disrupted, such as those who work night shifts, are at increased risk of cancer, but long-term human-intervention studies are difficult for ethical reasons. Animal models are the next best thing. In 2015, van der Horst showed that female mice that were genetically predisposed to develop tumors and that were exposed to light-dark cycles, which changed weekly, developed tumors early and were exposed to normal light. Gained 17% more weight than those kept in the conditions. His group has genetically altered the mice to either wake up early or late, and is investigating whether the mice live contrary to their natural rhythms to be carcinogenic. In collaboration with others, van der Horst is also studying the idea that chemotherapy may be more effective and have fewer side effects at certain times of day.

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