21 February 2019
A potential therapeutic target for lymphoma
Published online 22 June 2010
Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of cancer, accounting for ~40% of lymphomas in adults. Previous research has shown that the hepatocyte growth factor receptor, also known as c-Met, has oncogenic properties and might be an important target for the treatment of DLBCL. A group of researchers from the King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia, studied how the receptor works and its role in DLBCL by analysing samples from >250 patients with Middle Eastern origins.
c-Met was found to be overexpressed in nearly 75% of the DLBCL patients' samples, especially in those with a certain subtype called germinal centre DLBCL. By studying the receptor in vitro, the team determined that it is responsible for activating AKT and signalling pathways that lead to the growth, proliferation and survival of malignant cells. Adding a c-Met inhibitor caused a decrease in activated AKT and an increase in apoptosis in DLBCL cell lines.
Interestingly, the researchers also found that the overexpression of c-Met led to a better prognosis for the disease. These patients had an overall survival rate of 76.2% at 5 years, compared with only 57.5% in patients with low c-Met expression. The paper suggests this might be due to c-Met leading to the proliferation of lymphoma cells, making them more receptive to chemotherapy. Another theory is that the lymphoma cells might have retained the physiological growth control provided by c-Met.
- Uddin, S. et al. Inhibition of c-MET is a potential therapeutic strategy for treatment of diffuse large B-cell lymphoma. Laboratory Investigations. (7 Jun 2010). doi: 10.1038/labinvest.2010.108