Working in collaboration with an international team of researchers, Dr Vincent Keng Wee-keong, Assistant Professor of the Hong Kong Polytechnic University (PolyU)'s Department of Applied Biology and Chemical Technology, has developed a sophisticated model for studying "Malignant Peripheral Nerve Sheath Tumors" (MPNSTs), thus paving the way for further discovery of new genes and genetic pathways that may provide new therapeutic targets for related cancer treatment.
MPNST is a rare but aggressive type of tumor that is associated with extremely poor prognosis. It is believed that many genetic changes are required for both sporadic and NF1-associated tumor development, although the exact cause of MPNSTs is still not yet known. MPNSTs can occur sporadically or in the context of neurofibromatosis type 1 (gene NF1) tumor syndrome, a disease that occurs approximately one in 3,000 people worldwide. Of great concern is that around 10 percent of these NF1 patients will develop MPNSTs.
Due to the invasiveness and high metastatic occurrence of MPNSTs, current treatment regimes such as surgical resection, radiotherapy and chemotherapeutic treatments have proven to be ineffective. The current five-year survival rate for patients with metastatic MPNST is less than 25 percent. "We desperately need more accurate models of the disease in order to cure it", Dr Vincent Keng said.
In order to identify genes leading to MPNSTs, Dr Keng has been collaborating with researchers from University of Minnesota, Cincinnati Children's Hospital and University of Florida in the US; and the Institute of Predictive and Personalized Medicine of Cancer in Spain. The team has adopted The Sleeping Beauty transposon method, which is a powerful genetic tool and an unbiased approach, in a tissue-specific manner in mice.
Further analysis of these MPNSTs in this study uncovered 745 cancer candidate genes (both known and new genes). Genes and signaling pathways that cooperate in MPNST formation were also identified. In this study, the role of FOXR2 was demonstrated as an important oncogene or cancer-causing gene for MPNSTs development and turning off this gene drastically decreases the growth ability of these tumors. Researchers also found many of the MPNSTs have dual loss of NF1 and PTEN genes, both of which can suppress tumor formation.
Dr Vincent Keng has also previously shown that this pairing of lost genes causes MPNST formation in a paper published in Cancer Research last year. In his laboratory, research is continuing in both mouse models and human cell lines to obtain more effective therapeutic regimes for this deadly disease.
The MPNSTs research was published earlier this year in the international journal Nature Genetics (May 2013 Issue).Press Contacts
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