Jillian O’Connor stands in her living room laughing. A small boy hugs her leg, then takes off and disappears down the stairs to play with his older brother and sister. That was Declan. He turned four on February 1, 2019. The fact that his mother saw him blow out the candles on his birthday cake is extraordinary.

When Jillian was 18 weeks pregnant with Declan, she was diagnosed with metastatic breast cancer. She wasn’t expected to celebrate his second birthday. Two and a half years later, Jillian celebrated his fourth birthday with him—and still living life to its fullest.

The first thing that strikes you about Jillian is her smile. Next, it’s her insatiable enthusiasm for life. Then comes her contagious positivity. Hard not to think the latter alone is why she has made it so far against daunting odds. It may be anecdotal but Jillian definitely thinks, or rather knows, it’s the key.

“I am totally full of cancer, pretty much from my head to my toes,” said Jillian. “Every day I get is a blessing, ‘Oh, I woke up. Perfect!’ You just want to go at it as hard as you can, for as long as you can. Just being optimistic, I think helps. I really believe it helps.”

Jillian’s petite frame belies her light-up-the-room personality. She is gregarious with an enthusiasm that bubbles infectiously out of her. She talks about her cancer matter-of-factly. It is part of her life, but doesn’t rule her. She has other things to focus on—her precious family. The 35-year-old laughs and chats so easily about her life and her journey with cancer that it takes a second to realize how extraordinary her journey has been.

In 2014, Jillian was still nursing Landon, her second child, when she went to see her physician about a blocked milk duct. It turned out to be breast cancer. Doctors wanted to do CT scans to determine the extent of her cancer, but Jillian couldn’t. She was 18 weeks pregnant. Without treatment, she was told she wouldn’t survive to give birth. It was unfathomable. She had a three-year-old daughter and a one-year-old son at home. It was a devastating diagnosis but Jillian met it head on with her own special brand of optimism and determination.

Terminating the pregnancy was not an option for Jillian and her husband David. Her oncologist, Dr. Mark Clemons, told her she didn’t have to. He could provide a chemotherapy cocktail that would keep her cancer at bay without harming her unborn child. Jillian had a mastectomy and a dozen chemo treatments tailored to her special case. On February 1, 2015, she gave birth to a healthy baby Declan.

“I received chemotherapy right up until I delivered him. He was healthy—a wonderful birth weight. He was absolutely perfect,” said Jillian.

After Declan was born, Jillian had scans to see where the cancer was. It had spread, and had metastasized to her bones, liver, and lymphatic system. That was when she was given less than two years.

“Basically, they said, ‘We can’t give you a long timeframe. It’s stage X, so every day you wake up is going to be a gift,’” said Jillian, who stopped working as a nurse at the Queensway Carleton Hospital and became a patient there, receiving treatment at The Ottawa Hospital’s satellite cancer centre, the Irving Greenberg Family Cancer Centre. “Two years passed, then three, and then I passed four years this past summer. I’m hoping I’ll have another 40 plus years. I got a pretty doom and gloom diagnosis, but I continue to pull life off.”

Jillian has pulled life off in a big way. After all, when she brought Declan home from the hospital, she had three children under the age of three to look after. She poured herself into motherhood, enjoying every moment with them. Between weekly trips to the cancer centre for treatment, she was busy changing diapers, making meals, caring for, playing with, and loving her little ones.

Declan is back and clambers onto his mother’s knee—for about 30 seconds—before scrambling off onto the couch beside her. He is a typical four-year-old. His big sister Myla, who is seven, and brother Landon, who is five, appear, and the three play on the floor near their mom. Jillian chatters happily with them.

Jillian has celebrated all her children’s early-year milestones: learning to walk, talk, run, play, read, and become independent little people. Both Myla and Landon are now in school. Declan will be joining them in September. In mid-January, Jillian and David registered him for junior kindergarten. Nowadays, while the two older ones are in school, she and Declan have fun hanging out. They fill their days with activities that include volunteering at the school, as well as the more mundane household chores.

“I got a pretty doom and gloom diagnosis, but I continue to pull life off.”

Jillian is exuberant about life. She lives each day as it comes.

“She has, with all the help that modern radiotherapy and medical oncology can offer in Ottawa, in addition to her tremendous personality and drive, done amazingly well in a tragic situation for any young mom,” said Dr. Clemons. “At the same time, she has been involved in practice-changing research that is going to improve the care of patients—she continues to give.”

Over the past four years, Jillian has participated in clinical cancer trials with new therapies that have kept her cancer in check. When it spread to her brain a couple of years ago, she had whole-brain and CyberKnife radiation. Then she was put on new medication that can cross the blood brain barrier, which her regular chemotherapy couldn’t do. The medication halted new tumour growths in her brain. Her cancer is not getting better, but it’s not getting worse, either.

“I’m happy to stay status quo, because there is nothing I want to do that I can’t do right now,” said Jillian.“Status quo—I’m good with that. I feel great. I don’t have aches or pains or anything. I don’t have time to think about how I feel.”

Jillian sits on the floor laughing and playing with her three children. She looks at the little doll her daughter Myla shows her, and hands a ball to Landon. “I really think it’s the kids. They have so much to do with it, because they are so great. They are so fun. They keep me really busy and that’s half the fun. By the time I go to bed at night, I don’t think about cancer. I don’t think about tests coming up. I don’t think about that stuff because I’m too tired. So I think that is helpful.”

Dr. Clemons agrees.

“She is a gem, and her attitude of living life with true meaning is a humbling lesson for all of us,” said Dr. Clemons. “Too many people in society spend too much time moaning about the trivial, as well as things they can’t do anything about. Life is for living, and Jillian encourages people to do that—live!”

Whether it’s thanks to the innovative new treatment she receives or her uber-positive attitude, Jillian has surpassed the original two-year diagnosis by two-and-a-half years.

Dr. Clemons told her, “Whatever you’re doing, keep on doing it—obviously it’s working for you.”

And it is.

Three years ago, Sandy Patenaude was given the devastating news that she had stage 4 colorectal cancer. It had spread to her liver and lungs, and was inoperable. Sandy’s oncologist asked if she would like to go on a clinical trial, testing a new cancer stem cell inhibitor drug along with her chemotherapy.

“Cancer stem cell inhibitors, why not?” said Sandy who agreed to be part of the trial.

Dr. Derek Jonker, Medical Oncologist at The Ottawa Hospital, is leading the international trial for people with colorectal cancer, with the experimental drug napabucasin. He explained that cancer stem cells are the rare, immature cells in a tumour, which are often resistant to chemotherapy. They can give rise to the more mature cancer cells that make up the bulk of a tumour. Cancer stem cells are not the same as the normal stem cells that live in many healthy adult tissues and help with healing and repair.

“With chemotherapy, we can deliver treatment that can shrink the vast part of the cancer,” said Dr. Jonker, who is also an associate professor at the University of Ottawa. “Often the bulk of the tumour disappears, but what’s left is a small tumour with lots of these chemo-resistant cancer stem cells, which are able to spread and seed other places in the body. Often, we keep giving the same chemotherapy and find the tumour has regrown, but it’s not the same tumour it was when we started.”

Dr. Jonker is switching up the treatment to target the  cancer stem  cells that aren’t affected by standard chemo. In a previous randomized  clinical  trial he led , patients either  received a placebo or  napabucasin  to test its effectiveness at  inhibiting, or preventing,  the growth of the  cancer stem cells. The trial was carried out at  40  sites in Canada, Australia, New Zealand, and Japan. The  562  patients enrolled had advanced colorectal cancer  and chemotherapy no longer worked for them.

Looking at the results of the trial, Dr. Jonker said  they didn’t see much benefit in the group overall. “But when we looked at patients who had a  tumour  that  had characteristics of a high cancer stem cell (phospho-STAT3) over expression there was very significant improvement in their survival.”

Dr. Jonker presented his findings in October 2016 at the European Society for Medical Oncology, showing that where the cancer stem cell inhibitor didn’t work in all patients, there was an improvement in the survival of the 22 percent of patients who had  tumours  with high phospho-STAT3.  He said it’s “proof of principle that stem cells are an important target for cancer patients.” Napabucasin is now being combined in the  current trial  with chemotherapy to attack the cancer on two fronts  at the same time.

“We know  with results of the clinical trial that  the majority of  patients did not respond to it, but we have two patients here in Ottawa who  have responded and definitely developed benefit from the clinical agent,” said  medical oncologist Dr. Christine Cripps.

“I thought I’d be part of the trial, because I thought well, it’s new.”

Sandy is one of those patients who benefited.  Her tumours shrank,  and the surgeons were able to remove spots in her liver and the primary  tumour in her rectum.  Dr. Cripps said she believes that part of the success in keeping Sandy’s cancer at bay is the napabucasin she is taking as part of  the  clinical trial.

“A stem cell inhibitor works differently than traditional chemotherapy, in that it prevents new disease from  appearing,” said  Saara  Ali, research coordinator for clinical trials in gastrointestinal cancers. “The hope is that the pill [napabucasin] will prevent new disease from showing. And in Sandy’s case there hasn’t been new disease  since her treatment. Everything was there before, so it may be doing its job.”

Next steps: Dr. Jonker hopes to start  another clinical trial with the cancer stem cell inhibitor that will be used specifically for patients who have lots of phospho-STAT3 in their  tumour. These patients could be identified for the clinical trial with molecular testing, using The Ottawa Hospital’s Molecular Oncology Diagnostics lab.  This would target the patients presumed to be the most likely to benefit most from the drug.

“We would repeat our study, randomize those patients with  napabucasin  and a placebo, and if we can prove that  napabucasin is effective for them, then it would be an option for patients who have run out of all other treatment options,” said Dr. Jonker.

Dr. Cripps said that Sandy is a candidate for this next trial,  and her tumours  will be analyzed by the molecular lab to see  whether she has high phospho-STAT3 cancer stem cell expression. Regardless, Sandy will continue using the trial drug as long as it is working for her. And it is working. The mother of three adult children said  she’s busy doing a million things, playing euchre, the ukulele, skiing, hiking, biking, and enjoying life.

Although the connection between the immune system and cancer has been recognized for over a century, understanding how the immune system works against cancer has been the biggest challenge for scientists like Dr. Michele Ardolino.

Initially, efforts were made to stimulate the immune system to make it attack the cancer. But the game-changer was the discovery that there are key molecules, called immune checkpoints, on cancer cells that suppress the immune cells and prevent them from attacking the cancer. There are many types of immune cells. T-cells have been recognized as key immune cells and the ones that immunotherapy drugs have been designed to target.

“What we didn’t know before is that some of these receptors are present in other immune cells,” said Dr. Michele Ardolino, scientist at The Ottawa Hospital and assistant professor at the University of Ottawa. “What we discovered is that these receptors are present on another type of immune cell called natural killer cells.”

He said that even though most of the immunotherapy drugs target the T-cells to make them work better, not all cancer tumours are responsive to T-cells.

“But,” said Dr. Ardolino, “These tumours might be very effectively killed by natural killer cells. So, if we know what kind of tumour the patient has, we can design therapies to elicit the most effective immune response. Which in some cases could be a T-cell response and in other cases could be a natural killer response.”

“We now have a better idea of how the immune system suppresses cancer. This means that we can now target the mechanism that suppresses the immune system in a more specific way.”

“This is cool for a number of reasons,” said Dr. Ardolino. “We now have a better idea of how the immune system suppresses cancer. This means that we can now target the mechanism that suppresses the immune system in a more specific way. And we can elicit a stronger natural killer cell response against cancer.”

It is becoming widely recognized that not only is cancer unique to each patient, but the immune system is also unique to each person. Researchers and clinicians are realizing the importance of tailoring the immunotherapy not only to each person’s cancer but to their own unique immune system. It is a complex problem to give a drug that would have maximum therapeutic effect with the least side effects, to be as targeted as possible.

Dr. Ardolino recently published a breakthrough discovery that has potential to make immunotherapy treatments to work for more people, and more types of cancers.

In October 2018, immunologists James Allison and Tasuku Honjo were awarded the Nobel Prize in Medicine for their discoveries of immune checkpoint inhibitors, considered a landmark in the fight against cancer.

Ian McDonell was off-duty, walking along a bike path in August, when he saw men fighting. He called the police and tackled one of the men who tried to run away. But Ian’s courageous action is all the more remarkable because the summer before he was bedridden from cancer.

“I thought back to a year ago,” said Ian, “and there’s no way I would’ve even been out walking.”

Back up five years, Ian’s brother was dying of melanoma, and his father had just died of cancer. Ian’s wife insisted he see his physician to check out a mole on his back. It turned out to be an ulcerated nodular malignant melanoma–an aggressive form of skin cancer.

Ian had surgery to remove it and a lymph node from his left groin. Several weeks later, he had a lymph node removed from his armpit. Although he had no signs of cancer, considering his family’s history, Ian was high risk for relapse.

The 47-year-old Staff Sergeant with the Ottawa Police was referred to oncologist Dr. Michael Ong, a specialist in skin and urological cancers at The Ottawa Hospital. After discussing all options, Dr. Ong recommended Ian participate in a clinical trial using a targeted chemotherapy known to dramatically shrink melanoma, and being tested to improve cure rates.

“Immunotherapy does not directly affect the cancer itself. Instead, immunotherapy unmasks the cancer to your immune system.”

Ian took the treatment between November 2013 and August 2014 while still working full time, and continued intensive regular imaging scans after treatment to monitor for relapse. Ian was feeling very well at a standard monitoring visit in June 2017, but shockingly his CT and MRI scans showed sobering news. He had half a dozen tumours in his groin and abdomen, and three more tumours metastasized to his brain. Ian’s cancer was stage 4. Historically, patients with brain metastases live about four months.

Given the severity of the findings, Dr. Ong suggested an aggressive approach–a recently approved immunotherapy treatment.

“The idea of immunotherapy is not new. There have been clinical trials for decades. But only recently have we been extremely successful,” said Dr. Ong, who is also an assistant professor at the University of Ottawa.

Although, the connection between the immune system and cancer has been recognized for over a century, understanding how the immune system works against cancer has been the biggest challenge for scientists.

Initially, efforts were made to stimulate the immune system to make it attack the cancer. But the game-changer was the discovery that there are key molecules, called immune checkpoints, on cancer cells that suppress the immune T-cells, and prevent them from attacking the cancer. These immune checkpoints cloak the cancer from the immune system. New drugs called immune checkpoint inhibitors remove this cloak, and allow the immune system to naturally attack and destroy the cancer.

“The idea of chemotherapy is to kill off cancer directly,” said Dr. Ong. “There are potential side effects, because chemotherapy tries to poison the cancer. In contrast, immunotherapy does not directly affect the cancer itself. Instead, immunotherapy unmasks the cancer to your immune system by flipping some switches on T-cells, and the body’s own immune system does the rest.”

Immunotherapy is having the most success in patients with melanoma, like Ian. The first trial that demonstrated its effectiveness with this form of skin cancer was presented at an oncology conference in Chicago in 2010. The study results showed the median improvement in survival time was four months. Dr. Ong said, initially, the findings didn’t seem very impressive.

“It was just another clinical trial report, and four months didn’t sound like a long time,” said Dr. Ong. “But the reported improvement was the median change. What we didn’t realize until later was that while the immunotherapy didn’t work for 80 percent of patients, 20 percent of patients were actually cured of their metastatic melanoma. When data was looked at in 10 years, all of the responding patients were still alive.”

Since then, immunotherapies have been developed and tested in clinical trials that have increased the one-year survival rate for advanced melanoma from 25 to 80 percent.

Ian started on a combination of two immunotherapies, a big advance since 2010 and recently approved for use by Health Canada. He said the immunotherapy treatment is given intravenously in the chemotherapy unit at the hospital’s cancer centre. The whole process took two hours for each treatment, and Ian was scheduled for one dose, every three weeks for four treatments.

Ian did one round, then had CyberKnife radiotherapy treatment. High doses of radiation were directed at his brain tumours. He bravely continued with the second round of immunotherapy, but was so sick, he had to be taken off the treatment and started on steroid medications to slow down the immune system. Ian felt better, but his immunotherapy was on hold.

At the end of September, Ian had some new weakness in his face and there was worry about his cancer getting worse. It wasn’t. His scans showed one tumour had shrunk from 25 to 10 mm, and another tumour had shrunk from eight to four mm.

Dr. Ong said, “Looks like something good is happening here,” and recommended trying a single immunotherapy rather than two. Ian received the treatment in mid-November 2017. He found it extremely challenging again and was very sick.  All his treatments were stopped.

“But it did the trick,” said Ian.

Two months later in January 2018, Ian had a PET scan to assess the status of his cancer. A PET scan uses a radioactive sugar that highlights colour images where the cancer cells are. No colours lit up when Ian had the scan. Then he had an MRI, and there were no signs of any tumours in his brain. All three were gone. In April, he had a CT scan, and another again in July. Nothing showed up on the scans. He was tumour free. All trace of his cancer was gone.

At an appointment after the last scans, Dr. Ong told Ian that when he had first seen him in 2013, options for immunotherapy or targeted chemotherapy weren’t available. Four years later, thanks to incredible advances in immunotherapy, there was hope.

“In the last five years, we’ve gone from having very poor options to having many effective options for melanoma. That’s because cancer therapy continues to develop at a very rapid pace,” said Dr. Ong. “We, at The Ottawa Hospital, are constantly participating in practice-changing clinical trials. The standard of care is constantly changing, as it should. We are constantly trying to push the limits of cancer treatment.”

The Ottawa Hospital is a leader in cancer immunotherapy research, both in terms of developing new therapies and in offering experimental treatments to patients. Currently, there are 69 active cancer immunotherapy clinical trials being conducted at the hospital. Dr. Ong currently has 50 patients on immunotherapy clinical trials, but there are hundreds of patients on similar active clinical trials at The Ottawa Hospital.

People with melanoma skin cancer are young: 30 to 50. Melanoma that involves lymph nodes is very aggressive, and historically 50 percent of patients will have a relapse and spread of melanoma. However, new treatments, including immunotherapy, have between a 43 and 53 percent reduction in the risk of recurrence.  At The Ottawa Hospital, many patients are participating in a study to see if two immunotherapy drugs are better than one to reduce the chance of relapse even more.

As a result of successful immunotherapy treatments, patients like Ian are now faced with survivorship issues. Living without cancer.

Ian found he had to rethink what he wanted to do. He has been on sick leave from the Ottawa Police Services since August 2017 when the cancer returned.

“When the provincial exams for police services came up, I said, ‘I’m gonna write it, because I’ve got a bit of hope now.’ I wrote the inspector’s exam and I passed,” said Ian.

Immunotherapy has given the father of three his life back and a future to see his family grow up. He’ll also continue to tackle more crime.

The Ottawa Hospital is also conducting basic and translational research in immunotherapy. For example, Dr. Michele Ardolino recently made a breakthrough in understanding immunotherapy, which could allow this approach to work for many more people with cancer.

Read more about immunotherapy research.