Connecting cancer breakthroughs to clinical care

Sunnybrook’s Odette Cancer Centre in collaboration with Sunnybrook Research Institute focuses on translation research with the strongest potential for direct impact on clinical care. “Our translation goal is about helping to propel scientific breakthroughs in cancer research from the laboratory to the cancer clinic, to help extend life and quality of life for patients,” says Dr. Richard Wells, Director, Cancer Research Program, Sunnybrook Health Sciences Centre. “For example, scientists and clinicians – our researchers – collaborate on basic science related to better understanding of genetic and molecular events and markers to facilitate the development of novel, targeted therapeutics, and combine their expertise in imaging research for earlier detection, diagnosis, and more minimally invasive treatments,” he adds.

Dr. Robert Kerbel, a senior scientist at Sunnybrook Research Institute and Canada Research Chair in Tumour Biology, Angiogenesis and Antiangiogenic Therapy, who pioneered a concept called antiangiogenic ‘metronomic’ chemotherapy, is working closely with Odette Cancer Centre medical oncologists including Dr. Rena Buckstein, to approach translation of this concept into clinical care.

Antiangiogenic ‘metronomic’ chemotherapy is related to angiogenesis, and a metronomic chemotherapy approach. Angiogenesis is a natural process that happens in the body to heal wounds, and involves the growth of new blood vessels from pre-existing ones through a balanced series of on/ off switches. In cancer or tumour angiogenesis, these switches are no longer regulated properly by the body, and blood flow increases to the cancer, a process critical to its continued growth and spread. Greater understanding of tumour angiogenesis has led to developments in antiangiogenic drug therapies, shown to inhibit tumor growth by blocking blood flow to the cancer.

Metronomic chemotherapy, like a metronome, produces a steady, user-defined beat and involves close, regular, long-term administration of low-doses of drug therapies with a goal for better tolerance, reduced side effects and effective control in the treatment of several types of cancer. The thought is that metronomic chemotherapy targets the cells lining the blood vessels growing into the tumours, more than the tumours themselves, and thus acts as an antiangiogenic treatment.

Dr. Rena Buckstein, a hematologist at Sunnybrook’s Odette Cancer Centre and associate scientist, Sunnybrook Research Institute, conducted a Phase II clinical trial of high-dose Celecoxib (anti-inflammatory arthritis medication) and low-dose metronomic Cyclophosphamide therapy for patients with relapsed and refractory aggressive non-Hodgkin’s Lymphoma. Cyclophosphamide is a well-known chemotherapy drug usually given in higher doses. In contrast, in the trial it was given every day at very low doses, by tablet.

Dimitar Petkovski, 70, was diagnosed with relapsed non-Hodgkin’s Lymphoma in 2008 and is currently on this combination therapy. “So far I’m doing okay. I’m feeling good. Overall, my health is improving and I’m very pleased.” says Dimitar, who specifically chose Sunnybrook for his care.

Dr. Buckstein reports that Dimitar, like many patients in the published trial, is responding and tolerating the therapy extremely well with few side effects. “Although shrinking of the tumours is the goal, we are satisfied if we achieve stable disease for these individuals and help extend their lives.”

Says Dr. Kerbel whose foundational basic research in angiogenesis and antiangiogenic therapies is approaching translation to clinical care, “The dialogue between scientists and clinicians and our collaborations remain constant – towards improved quality of life.”