As we start this year, we would like to bring you up to speed on our recent progress in the discovery of new medications to treat brain tumours. Medical research is a long and trying process and each success must be celebrated. We think that being able to share this good news with you is the best present we could offer for the start of 2011.
The brain is without a doubt the most protected organ in the human body. On the outside, the skull can counter the majority of blows that could damage cerebral tissue, which could affect intelligence and basic physiological functions (heartbeat, breathing, etc.). In addition to this physical protection, the brain is also heavily protected internally with the help of an impenetrable barrier that controls access of blood products to the brain. Called the blood-brain barrier (BBB), this defense system plays an essential role in the maintenance of cerebral homeostasis by choosing which nutrients are needed to keep the brain healthy (glucose, amino acids and some hormones, among others), all the while preventing access to most unknown and potentially toxic substances.
Unfortunately, the BBB also prevents the entry of most medications and is therefore also a major obstacle in treating most diseases affecting the brain, particularly tumours.
CROSSING THE BARRIER
For the last 20 years, our lab has been working to solve the mysteries of the BBB in order to develop new therapeutic approaches that could cross the barrier, while also improving the effectiveness of brain cancer treatments. This research has allowed us to discover that certain peptides (derived from proteins) were able to interact with the receptors found on the surface of the barrier and, consequently, cross through it.
This is a major observation, as it allows us to see that these peptides could be used to transport cancer- fighting medications through the barrier, allowing them to directly act on brain tumours. Such an approach could revolutionize treatments for these cancers as, despite the major advancements in neurology in recent years, brain tumours remain extremely difficult to treat and survival over 11 months remains unlikely.
ENCOURAGING RESULTS
The therapeutic potential of this strategy is shown in the results obtained with a new medication that we have created, GRN1005, a derivative of the cancer-fighting agent taxol, developed by Angiochem. After demonstrating that this compound was active amongst animals, GRN1005 was the subject of two distinct clinical studies designed to determine the maximum tolerable dose, toxicity potential and in order to see preliminary signs of the drug's effectiveness.
Amongst patients who underwent intense treat-m ents to fight solid tumours that had metastasized to the brain, as well as patients with brain tumours (glioblastoma), the studies showed that GRN1005 had significant therapeutic potential.
The medication is active against metastases coming from various types of tumours, including lung cancer, breast cancer and ovarian cancer. Through the first phase of the clinical study, the rate of response for the patients who had received the maximum tolerable dose of GRN1005 was 42%.
More interesting still, certain patients suffering from glioblastomas saw their tumours completely eradicated.
NEW MEDICATIONS?
A deal worth more than $35 million was recently signed with American company Geron to further develop this promising new treatment. Phase 2 of the clinical study will begin this year, using patients with metastases to the brain stemming from lung or breast cancer.
The ultimate goal of medical research remains the discovery of new ways to improve the population's health, particularly amongst the sick. As the Director of Neurosurgery at the University of Montreal's Hospital Centre and head of Prevention and Chair of Prevention and Treatment of Cancer at the Université du Québec à Montréal, I would like to express our delight in seeing a new family of medications joining the fight against brain cancer reach advanced clinical trial phases. It is our way of wishing you a Happy New Year!
Dr. Richard Beliveau holds the chair in cancer prevention and treatment at the University of Quebec in Montreal.
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