Syndicate content

Archive - Mar 23, 2015

New Approach Targets Familial Stomach & Lobular Breast Cancers; GPCR and Cytoskeleton Proteins Found Strikingly Abundant in E-Cadherin-Minus Cells Such As These Cancer Cells

Deadly familial stomach and lobular breast cancers might be successfully treated at their earliest stages, or even prevented, by existing drugs that have been newly identified by cancer genetics researchers at New Zealand's University of Otago. The researchers, led by Professor Parry Guilford, show, for the first time, that the key genetic mutation underlying the devastating conditions also opens them to attack through drug therapies targeting other cellular mechanisms. There is currently no treatment for this kind of gastric cancer other than surgical removal of the stomach as a preventive measure in those identified as carrying the mutated gene. Lobular breast cancer is hard to detect by mammography and mastectomies are also undertaken by some carriers. The researchers' new findings were published online on March 16, 2015 in Molecular Cancer Therapeutics. The team used genomic screening to search for vulnerabilities in the cancer cells that lack the tumor-suppressor protein E-cadherin. The genetic mutation that causes this protein to be lost is common in hereditary diffuse gastric and lobular breast cancers. E-cadherin is not a traditional drug target for these forms of cancer because the protein is present in healthy cells, but absent in malignant ones. However, Professor Guilford and his team predicted that its loss might create other vulnerabilities in these cancer cells. Professor Guilford says the research team used an approach of searching for “synthetically lethal” combinations of E-cadherin loss with inactivation of other proteins, which together cause cell death. After conducting a genome-wide functional screening of non-malignant human breast cells with, and without, E-cadherin loss, they identified a large number of such vulnerabilities that can be targeted by existing drug compounds.

Funding Allocated for Clinical Trial of Low-Dose Ketamine for Treatment of Rett Syndrome

A surgical sedative may hold the key to reversing the devastating symptoms of Rett syndrome, a neurodevelopmental disorder found almost exclusively in females. Ketamine, used primarily for operative procedures, has shown such promise in mouse models that Case Western Reserve and Cleveland Clinic researchers will soon launch a two-year clinical trial using low doses of the medication in up to 35 individuals with Rett syndrome. A recently allocated $1.3 million grant from the Rett Syndrome Research Trust (RSRT) represents a landmark step in area researchers' efforts to create a true regional collaboration that capitalizes on the diverse expertise of scientists and clinicians all dedicated to improving the lives of individuals struck with this and other autism spectrum disorders (ASDs). Dr. David Katz, a neuroscientist at Case Western Reserve, and Thomas Frazier II, Ph.D., Director of the Cleveland Clinic Center for Autism, led creation of a Northeast Ohio consortium three years ago to encourage research partnerships among basic scientists and clinicians. Cleveland Clinic, University Hospitals, and Case Western Reserve each contributed seed funding; the consortium also is affiliated with the university's International Center for Autism Research and Education. Rett syndrome, which occurs in roughly 1 of every 10,000 female births, leads to a constellation of symptoms mirroring those of autism, Parkinson's disease, cerebral palsy, and anxiety disorders. Its presence does not manifest itself until after birth; symptoms often do not begin to appear until the child reaches six months of age. Development slows, communication skills decline, and motor skills are also affected. The rate of growth of the head decreases, and seizures and/or disruptions in breathing patterns are common.