The fat sucked out of the body and modified with it CRISPR tool for genetic modification could be used for cure cancerat least according to a study in mice and suggestions of transplanted human tissue, however it remains to be seen whether the experimental therapy would be safe and effective in people.
The new study found that white fat extracted from the body can be genetically reprogrammed with the CRISPR tool to mimic brown fat and then introduced into rodents to shrink tumors.
White fat stores excess energy in the body, while brown fat warms the body by breaking down blood sugar, or glucose, a function that could be used to deprive tumors of the nutrients they need for growth; the study tested this idea using white fat extracted from both humans and mice, as well as tumors transplanted from humans and mice.
The accumulation of white fat in the body increases the number of cells that have the potential to turn into cancer, which partly explains why weight gain is linked to cancer risk.
However, a 2022 study involving mice and a human cancer patient suggested that while white fat is known to increase cancer risk, brown fat may actually be shrinking tumors, with cold temperatures prompting the increase in cancer risk. Glucose uptake by brown fat into overdrive and starved cancers of fuel, research has shown.
What the new CRISPR tool study is based on
The new studywhich has been uploaded to the prepress server bioRxiv on March 29 and has yet to undergo peer review, has essentially exploited this phenomenon in a new cancer therapy.
A team of geneticists at the University of California, San Francisco (UCSF) developed the therapy in mice and called it modulating fat transplantation (AMT). The approach involves converting white fat to a brown-like ‘beige’ fat outside the body by activating the genes required for ‘browning’.
The team tested AMT in mouse models of breast, colon, pancreatic and prostate cancer and found that implanting beige fat caused all of these tumors to shrink in half in size.
Nadav Ahituv, a professor in the UCSF School of Pharmacy and senior author of the study, told Live Science that AMT “could work very well with other therapies,” but “more work needs to be done” to monitor whether the beige fat implants raise body temperature to fever pitch or cause other worrying side effects. (Ahituv has filed a patent for AMT.)
Yihai Cao, a cancer biologist at the Karolinska Institute in Sweden who was not involved in the study, said AMT is a “very interesting approach” because, unlike most cancer therapies, it does not directly target the tumor , which is often difficult to reach. However, “the long-term impact on tumor growth suppression remains to be seen,” said Cao, senior author of the 2022 cold exposure study.
Brown fat is normally found in the necks of mice and humans, but in Cao’s 2022 study, breast, skin and pancreatic cancers were suppressed despite being far from the fat. Ahituv and his team found that beige fat implanted in the rear could have a similar long-distance effect, at least on breast cancer. In their other experiments, the team transplanted beige fat into mice near transplanted human colon, pancreatic and prostate tumors, so they have yet to confirm that fat can also exert long-distance effects on those tumors.
AMT was designed to be easily adopted in humans. White fat is commonly extracted via liposuction and reimplanted during plastic surgery. However, because cold exposure doesn’t involve invasive surgery, it may be easier to adopt than AMT, Cao said.
But the fat can be implanted during pre-specified cancer surgeries, such as mastectomy, Ahituv noted. And gene editing is commonly used in gene therapy and a cancer treatment known as CAR T-cell therapy, so Ahituv doesn’t expect the use of the CRISPR tool in AMT to hinder the therapy’s adoption in human patients .
AMT has only been tested in mice and in laboratory-grown breast tumor samples from human cancer patients, so its efficacy and safety in humans can only be speculated until clinical trials are performed. Some studies suggest that, in cancer patients, brown fat may sequester nutrients from healthy cells and contribute to cachexia, a wasting syndrome associated with the disease. The researchers didn’t observe the weight loss in the mice over a six-week period, but Ahituv said cachexia could appear later, so longer studies are needed.
Researchers will need to “figure out how much fat we implant in each patient and how much is too much,” Ahituv said. And it may be pertinent to remove the implants after some time or install an “emergency switch” to prevent them from sapping nutrients to healthy cells, he added.
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