Environmental Cancer Prevention
One of our major community intervention and cancer prevention research projects is “Evict Radon”, an interdisciplinary program involving scientists from across the world and led by the Robson DNA Science Centre’s Dr. Aaron Goodarzi.
The goal of this project is to prevent alpha particle radiation exposure from radon gas as a source of Canadian lung cancer, and define human populations who are especially susceptible to the negative effects of long terms radon / radiation exposure. We are being impactful by defining actionable strategies to prevent radon exposure, the 2nd leading cause of lung cancer responsible for 10,000-40,000 Canadian cancer deaths each decade, and enabling early cancer detection by establishing a mechanistic basis for predicting lung cancer risk from exposure data and functional biomarkers.
For more information, please visit = www.evictradon.ca. A selection of news articles and videos on this project – including Dr. Goodarzi’s recent TEDx talk, may be reached by clicking the images below.
Novel Anti-cancer Therapeutic Approaches
Blood Cancer, specifically multiple myeloma, arises from white blood cells that would normally produce antibodies within our immune system. Multiple myeloma is the second most common type of blood cancer and, sadly, has a median survival of only about 5 years since current forms of treatment are largely ineffective, with most patients relapsing. Oddly, multiple myeloma shows a bias towards occurring in males and even certain ethnicities. The laboratory of Dr. Nizar Bahlis has determined that the way in which multiple myeloma cells rewire their DNA repair systems may be key to novel therapeutics for this disease. His group have found that a type of drug known as a ‘proteasome inhibitor’, specifically Bortezomib, can sensitize multiple myeloma cells to other anti-cancer treatments. This combined therapy has dramatically improved therapeutic outcome for multiple myeloma – in the case of some patients causing complete remission of their disease. These promising experimental therapies are now at the level of clinical trials being carried out by Dr. Bahlis and colleagues, and continue to be refined through collaboration between Dr. Bahlis and other members of the genome instability and aging research group.
Whether or not cancers express genes necessary to respond and repair DNA damage properly can have an enormous impact on their ability to respond to radiation and/or chemotherapy. Of particular interest to our group is the gene encoding ataxia-telangiectasia mutated (ATM), which is essential for the cellular response to DNA damage caused by radiation and many chemotherapeutics and is mutated of altered in a number of cancers. The laboratories of Dr. Susan Lees-Miller and Dr Gwyn Bebb, working together, have shown that Mantle Cell Lymphoma (MCL) and gastric cancer cells with low levels of ATM (or that have been treated with a drug that inhibits ATM) are particularly sensitivity to olaparib, an anti-cancer drug called a PARP inhibitor that is currently in clinical trials.
Their studies suggest that PARP inhibitors may have therapeutic potential in the treatment of ATM-deficient cancers and also suggest that inhibition of ATM enzymatic activity in combination with PARP inhibition may be of particular benefit in cancers where the p53 gene is deleted or mutated. Since p53 is mutated or deleted in approximately half of all human cancers, their results could be applicable to a wide range of tumor types.
It is of great importance and interest to identify predictive markers of a positive response to radiation therapy for a variety of cancers. This is so that radiation and chemotherapy can be better targeted to the molecular characteristics of the particular tumour, improving patient outcome and avoiding non-productive use of radiation. This knowledge can also inform whether adjuvant therapies may be useful to combine with radiation or chemotherapy to improve patient responses.
The laboratories of Dr. Susan Lees-Miller and Dr. Corinne Doll are currently working together to determine what happens (in terms of cellular and patient outcome) during radiation therapy when the gene encoding the Phosphatidyl inositol 3 kinase (called PIK3CA) is mutated in cervical cancer. Their team has shown that early stage cervical cancer patients respond less well to radiation and chemotherapy treatment when their cancer has mutations in PIK3CA gene that increase the activity of PI3KCA enzyme it encodes. Importantly, they are testing whether drugs that inhibit PIK3CA (and which are already in clinical trials for other cancers) will block the activating effects of the PIK3CA mutation and confer better response in cervical cancer patients to radiation and chemotherapy.
Breast cancer is the most common cancer affecting Canadian women. Although treatment options vary with tumour subtype and stage, chemotherapy plays a prominent role. In particular, chemotherapy using drugs such as doxorubicin and etoposide, which target the essential cellular enzyme DNA topoisomerase II (topo II), are effective at decreasing the rate of relapse and cancer-related mortality in women with early-stage breast cancer, while significantly slowing disease progression and increasing overall survival for women with metastatic disease. The success of therapy, however, can be affected by a number of factors, including interaction with common prescription and over-the-counter medications.
Aspirin has been in use for more than a century and it is estimated that more than 40,000 tonnes are consumed annually worldwide. Dr. Ebba Kurz and her colleagues have recently discovered that salicylate, the main active breakdown product of aspirin, directly inhibits topo II, reducing the effectiveness of several widely used chemotherapeutics at killing cancer cells grown in the laboratory. They are now systematically investigating whether salicylate (and related drugs) decreases the effectiveness of these common chemotherapeutics in animal models of breast cancer. Given the widespread use of aspirin and related drugs, this research may help guide physicians on the clinical use of these drugs during chemotherapy.