Leighl and Sacher
Drs. Natasha Leighl (L) and Adrian Sacher are the successful principal applicants of the first two Princess Margaret Grand Challenges. (Photos: UHN)

A series of bold, innovative and high-impact projects launching at the Princess Margaret Cancer Centre are advancing cancer diagnoses and treatments to cure more patients and improve quality of life by moving beyond chemotherapy.

The series, called Princess Margaret Grand Challenges, focuses on four key directives:

  • Detecting cancer early and intercepting it before symptoms, while still curable  
  • Thinking beyond chemotherapy towards more precise, customized therapies that effectively target cancer to each individual patient, without the harsh side effects of chemotherapy
  • Reimagining and redesigning the cancer patient experience by maximizing digital intelligence and embracing augmented human intelligence
  • Solidifying the human touch in cancer care by infusing comfort and joy into every interaction, with particular focus on equity and access, navigation, diversity, ambience of the centre, patient engagement, inclusivity and supportive communication 

The series sets the stage for the Princess Margaret moving boldly towards precision medicine and tailored individualized treatment plans for each patient. 

After a call for project proposals in July, two projects were selected to help improve cure rates for lung cancer, one of the deadliest cancers in the world.

Both projects – one led by Dr. Natasha Leighl, the other by Dr. Adrian Sacher – test an exciting new procedure called liquid biopsy, in which Princess Margaret is a global leader.

In developing this next-generation sequencing technology, scientists can now pinpoint quickly, accurately and less-invasively whether the cancer is active in each individual patient with a simple blood test. In contrast, with various imaging scans, it may take months to detect whether a tumour is shrinking.

Using liquid biopsy to intercept lung cancer early

Although 40 per cent of patients present with lung cancer in the early stages of the disease, the risk of relapse remains high for those that undergo surgery with curative intent.

Identifying those at high risk of recurrence quickly and effectively and offering further treatment before the cancer spreads to other organs could potentially cure more patients.

Over the last several years, scientists have discovered that tumours can shed small amounts of DNA fragments into circulating blood. These fragments are called circulating tumour DNA or ctDNA, and mirror the same genetic mutations as in the actual tumour. 

Currently, early stage lung cancer patients enter an observational period after surgery. Dr. Leighl, Medical Oncologist, and her colleagues at the Princess Margaret, are studying how we can now harness liquid biopsy to detect the presence of circulating tumor DNA even after surgery and predict those at high risk of recurrence that may benefit from further therapy, such as chemo-immunotherapy, leading to increased cure rates in early stage lung cancer patients.

Additionally, by identifying those at high risk of recurrence, those with low risk can avoid further treatment, thus minimizing any debilitating side effects. 

Her study will use liquid biopsy technology to monitor early stage lung cancer patients before and after surgery, with regular blood tests, to test for ctDNA or indications of residual disease.

"Up until this point, there have not been enough studies that help us make this new technology a part of our standard of care," says Dr. Leighl, Lung Site Lead for Medical Oncology and Principal Applicant of the project. "Our ability to use this as an everyday test is an important future direction that could really impact the lives of our patients and increase the chance of cure."

The study promises a personalized approach to determine individual cancer risk, resulting in a potentially curative approach for those with early stage lung cancer.  

Moving beyond chemotherapy by monitoring response to immunotherapy

Immunotherapy is revolutionizing the way we treat lung cancer. When it works well, it can produce remarkable responses and extend survival for patients with advanced cancer.

The challenge is that it only works for a subset of patients.

Right now the solution is to treat advanced lung cancer – cancer that has spread outside of the lung to other areas of the body – with immunotherapy and chemotherapy, giving both treatments initially to increase the chances that the patient will respond.

However, adding chemotherapy to immunotherapy increases debilitating side effects such as nausea and hair loss.

Identifying patients who could benefit from immunotherapy alone would help patients avoid these chemotherapy-related side effects. 

Dr. Sacher and co-investigators are looking at using liquid biopsy to determine early on who is responding well to immunotherapy to avoid chemotherapy altogether.

Their study will look at treating advanced lung cancer with a combination immunotherapy of two drugs. After three weeks, patients will have their blood analyzed for ctDNA using the liquid biopsy technology to determine if the cancer is responding to treatment. 

If patients aren't responding, their treatment will be intensified based on each patient's individual or personalized ctDNA residue found in their blood tests. 

The novelty is that rather than using a one-size-fits all approach, each patient receives a personalized blood test based on their own tumour profile and response. 

"I imagine a future where we use this technology to provide a real-time stream of data on how someone's cancer is responding to treatment so we can adapt quickly and in a personalized way," says Dr. Sacher, Medical Oncologist, Princess Margaret Cancer Centre and Principal Applicant of the project.

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