The researchers found that an inflammation-related molecule called RIP1 is commonly found in high levels in glioblastoma, the most common primary malignant brain tumour in adults. In the study, the researchers examined tumour tissues from 92 patients to determine the distribution of RIP1 in each.
The study could provide a new target for therapeutic drugs for glioblastoma patients who have a high level of RIP1 in their tumours coupled with NF-kB activation. “This is the first report of high RIP1 levels being associated with any type of cancer,” said Amyn Habib, the study’s senior author. “Our data suggests that increased expression of RIP1 could serve as a marker to identify patients who have a significantly worse prognosis and who will likely be resistant to chemotherapy.”
Glioblastoma multiforme (GBM), a cancer of the supportive tissue of the brain, is resistant to treatment. GBM can infiltrate the brain extensively and sometimes become large before turning symptomatic. The median survival of patients with GBM is about 15 months after diagnosis, even with radiation and chemotherapy treatments.
One of the next steps is to determine whether these patients may respond better to drugs targeting the NF-kB network. The protein RIP1 is a component of the complex NF-kB signaling network – a family of proteins that play a key role in inflammation-induced cancer. There are many drugs currently available that target these proteins.
Another significant finding of the study is that the protein RIP1 regulates the function of p53, a tumour suppressor gene that inhibits the growth of tumours. “RIP1 activates NF-kB and then that increases the expression of a gene called mdm2, which inhibits the p53 gene,” Habib said. “Inhibition of p53 allows cells with damaged DNA to proliferate and potentially to become cancerous.”
Habib cautioned that the results are preliminary and more research is needed to investigate possible therapeutic strategies. “We have found a correlation,” Dr. Habib said. “If RIP1 is increased, patients do worse; however, we do not know whether this molecule has some causal role in pathogenesis.”
MEDICA.de; Source: UT Southwestern Medical Center