The power of precision medicine for cancer – a speech from BC Cancer Consortium co-lead Dr. Marco Marra

On October 30, 2024, members of the Marathon of Hope Cancer Centres Network and leadership from the Terry Fox Research Institute held a reception for Members of Parliament and other government representatives on Parliament Hill. The event was sponsored by MP Pam Damoff. Several Network members gave addresses, including Dr. Marco Marra, one of the co-leads of the BC Cancer Consortium. Dr. Marra is a professor in the Department of Medical Genetics and member of the Michael Smith Laboratories at the University of British Columbia and a distinguished scientist at Canada's Michael Smith Genome Sciences Centre at the BC Cancer Research Institute. He is also the Terry Fox Leader in Cancer Genome Science and the co-founder and the co-lead of the Personalized OncoGenomics (POG) program. On Dec. 18, 2024, Dr. Marra was named an Officer of the Order of Canada.

Here is a transcript of the speech he delivered during the event.

We now know that cancer is not one disease, but hundreds.

We also know that within each type and subtype of cancer, enormous diversity exists.

High-resolution cancer genome analysis, in which all the genetic material of cancer and normal cells is read through the process of DNA sequencing, has shown that many, many differences in the genetic code exist, even between patients who are thought to have the same type of cancer.

The number of DNA sequence differences between the genomes of healthy people is similarly enormous. For example, the copy of the genome that you inherited from your biological mother has millions of differences from the copy of the genome that you inherited from your biological father.

We cannot predict all of the DNA sequence changes that we know are present in the tumour and normal genomes of a cancer patient, but we don’t need to guess what they might be. Instead, we can very precisely read them all out, using powerful DNA sequencing instruments and high-performance computing.

In the Marathon of Hope Cancer Centres Network, we capture essentially all of this genomic diversity, in both cancer and normal cells. But our objective is not only to map the extensive genomic diversity that underpins how cancer grows and becomes resistant to treatments.

Instead, with knowledge of the exact DNA changes in hand for each patient, our objective is to first sift through these changes to find those that result in cancer cell vulnerabilities, and then target these vulnerabilities with treatments that physicians can use to kill the cancer cells. To use an analogy, we aim to identify the kryptonite we can use to defeat the cancer cell “superman”.

This is not fantasy. We know it is possible. For example, there is the case of a patient who was diagnosed with colorectal cancer in their 60s. They endured numerous treatments, but even so their cancer continued to grow and spread.

At the time their tumour was analyzed, they had experienced many different treatments and had decided to decline further cancer treatments due to their ineffectiveness and toxicity, looking for palliative options instead.

Imaging revealed that cancer had spread to many locations throughout the body. Genomic analysis of a metastasis at the base of their spine eventually revealed a very specific genomic vulnerability that could be targeted using a blood pressure medication. Within weeks after taking this medication, imaging revealed they were largely cancer-free. Their oncologist was amazed.

This occurred more than 8 years ago, and just last month, they gave a keynote address at our Precision OncoGenomics retreat in BC. They are still with us, and still taking blood pressure pills.

There is also the case of a terminal cancer patient with no remaining standard treatment options. Again, genomic analysis revealed a vulnerability that could be targeted using a diabetes drug. They too are still with us, 8 years later.

And the case of a late-stage lung cancer patient, who had also exhausted available treatment options. Genomic analysis of their cancer revealed two genes which were fused together.

This fusion inappropriately activated cancer-causing cell machinery, which was targeted using a drug approved for different cancers, but not theirs.

The drug worked, shrinking their lung tumour and extending the duration and the quality of life. Importantly, the genomic and clinical data they shared with researchers allowed the same drug to be successfully used in subsequent liver and pancreas cancer patients with very similar fusions, also detected using genomic analysis.

Surprisingly, we found that the fusion we originally detected in our lung patient was a hallmark feature of a subtype of pancreas cancers, and the drug also works for them and is now routinely used.

There is also the case of a very young patient with a rare cancer. With no standard treatment options, genomic analysis indicated that they would respond to immunotherapy. They did.

Or the patient who was on state-of-the-art but ineffective immunotherapy. Genomic analysis indicated their tumour had a vulnerability that could be targeted using an old, off-patent chemotherapy. Within a month, the massive tumour on their neck had melted away.

We have many similar examples, but there are other areas of precision cancer medicine where genomic analyses can contribute.

Genomic analysis has changed diagnoses, allowing cancer patients to receive the correct treatment for their disease. And, in approximately 15% of POG cases, genomic analysis has revealed cancer predisposing mutations in cancer patient’s normal DNA. This is very important, because once such mutations are known, members of the patient’s family can be tested to see if they too carry the mutation. If so, they can be carefully monitored so that if they do develop cancer in the future, it can be detected early, treated effectively and even cured.

These examples illustrate our objectives and the impacts we can have through the TFRI’s Marathon of Hope Cancer Centres Network. Not only in Vancouver, or Toronto or Montreal, but across the country. The way forward will of course be challenging, as are all such bold initiatives, but the benefits of extending the Network forward in this way will be profound for patients, their families, caregivers and stakeholders across the country. Building on the Network established by the TFRI, we now have the opportunity to explore new research domains for Canada that will lead directly to precision cancer genomic medicine and I, for one, am thrilled to be involved in this incredibly worth-while and exciting Canada-wide initiative.  

Thank you.