New combination drug inhibits cancer growth

 
European grant awarded to a spin-off company from Maastricht University for further development
 
Maastricht, December 2013 
 
Maastricht University researchers have developed a drug that can fight a tumor by acidifying it without adverse side effects. The effect of this drug, which contains two components, is even greater in combination with chemotherapy and radiation. This week, a spin-off company from Maastricht University, DualTPharma (www.dualtpharma.com), together with a Belgian company (www.sepspharma.com) and the University of Aachen received a European grant (GCS Fund, Interreg), to further develop this drug for use in patient care within two years.
 
Recently, two articles have been published in the well-known scientific journals Radiotherapy and Oncology (Dubois et al, 2013) and Journal of Medicinal Chemistry (Rami et al, 2013) that show that when a particular protein that helps the cancer cell survive is blocked by a molecule, the cancer cell dies. This protein, CA-9 (Carbonic Anhydrase-IX), ensures that acid levels remain neutral, which allows the cancer cell to survive. An increased presence of this protein in a tumor often means a poor prognosis for the patient. The Maastricht team, under the direction of Prof. Philippe Lambin, has shown that because of CA-9’s role in acid regulation, this protein is a perfect target for fighting cancer. The developed drug is a CA-9 inhibitor that acidifies the cancer cell and kills it without damaging the normal tissues.
 
In recent years, scientists from Maastricht University, Montpellier and Florence have developed various CA-9 inhibitors to investigate their therapeutic effects. The protein CA-9 is prominent in 70% of all solid tumors and is not present in normal cells. It is therefore a promising target for development of new treatments. Ludwig Dubois, one of the researchers, explained: ‘our approach is unique because this drug is based on a double working mechanism: (1) increasing the acidity of tumor cells and (2) making the tumor more sensitive for treatment. This drug can be used on its own or parallel to the standard treatments (radiotherapy and chemotherapy).’
 
This multifunctional drug will be further developed and marketed via DualTPharma, a spin-off company from Maastricht University that was started earlier thanks to a Pre-Seed Grant from ZonMw-NWO. Professor Lambin, the team leader and one of the inventors, explained: ‘The great difficulty of a cancer treatment is to tackle the tumor cells without affecting normal cells. We are convinced that we have found the Achilles heel of most cancer cells: they produce a lot of acid that is neutralised by the protein CA-9. If we can disturb this process with a specific molecule with two active parts, we see that the cancer cell is killed without toxicity: the cancer cell is more acidic and can no longer function. Think of a car in which the emissions come into the compartment instead of being emitted outside.
 
Dr. Patricia Soetekouw (Medical Oncologist, azM), who will be responsible for the first clinical study, continued: ‘the beauty is that the medication can be given orally. SEPS Pharma will be responsible for the optimization of the oral formulation.’
 
The CEO of DualTPharma, concluded: ‘We are pleased that GCS has granted our project funding. For us, this project is an important step towards a first clinical study, which we want to start in 2015.