New award to combat drug-resistant cancers
7 June 2010
PTC Therapeutics, Inc. will use the funds to develop drugs that target Bmi-1 - a protein that has been implicated in a variety of cancers because of its ability to allow cells to self-renew. In particular, there is significant evidence that high levels of Bmi-1 are a major driving force in glioblastoma, the most common and aggressive form of human brain tumour. Bmi-1 has also been shown to contribute to drug resistance and treatment failure.
Recent studies have shown that tumours contain a small number of cells referred to as 'cancer stem cells' that are involved in initiating tumour growth and progression. These stem-like cells are more resistant to chemical and radiation therapies than are other tumour cells. So even though chemo- and radiotherapies can be effective at shrinking tumours, these stem-like cells that are resistant to therapy can persist and ultimately cause tumours to recur.
Bmi-1 acts by switching off regulatory pathways inside the cell that would normally stop the cell from reproducing and it has been shown to be essential for stem-cell survival. Drugs that inhibit Bmi-1 are expected to make cancer stem cells susceptible to treatment and improve patient outcome.
"We are pleased to receive this grant from the Wellcome Trust because it supports our ongoing commitment to identifying novel treatments for serious and life-threatening diseases," said Stuart W Peltz PhD, President and Chief Executive Officer at PTC Therapeutics. "Compounds that selectively reduce Bmi-1 levels have broad therapeutic potential in treatment of drug-resistant cancers, such as glioblastoma, a cancer where current therapies extend life by only months."
The team will focus on looking for drugs that block the expression of the Bmi-1 protein, without affecting the production of other proteins inside the cell. The programme has already given some promising results and is currently at the stage of identifying a lead candidate to take forward. The ultimate goal is to identify a drug candidate that could be taken orally for the treatment of chemotherapy-resistant cancers.
"PTC's elegant approach to tackling chemotherapy resistance takes us into a truly novel area of research," said Dr Rick Davis of the Wellcome Trust. "A successful drug candidate would address a huge unmet medical need."
The Wellcome Trust launched the Seeding Drug Discovery funding initiative in 2005 to facilitate early-stage small-molecule drug discovery in areas of unmet medical need. After a comprehensive review of the initiative, the Trust has recently announced a five-year extension to the scheme with an injection of £110 million.
Image: Glioblastoma cells. Credit: Alex Gray, Wellcome Images
