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New Investigator hopes oxygen-enhanced cancer tumours will improve treatment outcomes

This project has been completed

While survival rates for many cancers have improved over the last decade, cure rates for some forms of the disease – such as pancreatic cancer – remain as low as just two to three per cent.

“The survival rate for pancreatic cancer is abysmal,” says Dr. Ralph DaCosta, a molecular imaging scientist, noting that around 5,000 Canadians are affected by the disease each year. “One of the main reasons that I picked this particular cancer to study was because I thought we could bring a real level of innovation and new knowledge to understanding this complex tumor microenvironment.”

He’ll use a $450,000 New Investigator award from TFRI to try to find new and innovative ways to study the complex tumor microenvironment to develop new treatment strategies for pancreatic cancer and prevent deadly tumour recurrences in patients from his laboratory at Toronto’s Princess Margaret Cancer Centre, UHN.

Radiation and chemotherapy can be a very effective treatment for many cancers, but are often unsuccessful in treating pancreatic cancer. DaCosta’s research team has learned that advanced pancreatic tumours are often very “hypoxic”. This means they are low in oxygen, which decreases the efficacy of treatment, and increases the likelihood tumours will grow and spread aggressively.

Further, the team discovered in animal models of pancreatic cancer that high-dose radiation therapy can actually increase tumour hypoxia, change the invasive behaviour of tumour cells, and modify the tumour microvasculature and microenvironment. The result? It’s harder to kill cancer cells.

But there’s hope: Dr. DaCosta and collaborators in the Leslie Dan Faculty of Pharmacy (University of Toronto) have developed a new injectable nanoparticle formulation comprised of manganese dioxide that generates oxygen in vivo, and makes a tumour less hypoxic. When used in conjunction with traditional radiation, early results suggest cancer cells can be killed more easily using a much lower treatment dosage.

“The clinical impact is pretty profound if we can get this right. If you give a patient the nanoparticles, and make the tumour more oxygenated, you could be just as effective at killing tumour cells with a much lower radiation dose, and also reduce unwanted toxicity of the therapy to the patient,” Dr. DaCosta explained.

Drs. Bradley Wouters and Rob Bristow, co-principal investigators of TFRI’s Hypoxia Program and senior scientists at UHN, will mentor Dr. DaCosta for the duration of the three-year award.

“The work [he is] doing in pancreatic cancer…will bring new approaches to understanding the hypoxic environments of other cancer types under investigation in this program including cervix, head and neck, and prostate,” said Dr. Wouters. “I look forward to [his] future contributions to our Institute’s scientific success.”

DaCosta says he was so excited to win the TFRI NI award he almost fell out of his chair.

“It’s just great all-around and we’re thrilled, absolutely thrilled,” he said. “And the best part is if we can get this to work in the pancreas, we could apply the same methodology to other solid tumours.” 

Mentoring Program: The Terry Fox New Frontiers Program Project Grant in Research Pipeline for Hypoxia-Directed Precision Cancer Medicine
Mentors/PIs: Drs. Bradley Wouters and Robert Bristow