What is Personalized Onco-Genomics?

Personalized Onco-Genomics (POG) is BC Cancer’s flagship study in precision medicine. It is an experimental clinical trial that deploys whole genome analysis to inform individual treatment planning for patients.

The process involves sequencing the genome of participating patients who have metastatic cancer in an effort to determine what may be driving their particular type of cancer. Genomes are mapped twice for each participant: once with normal cells and once with biopsied cancer cells. The sequences are then compared in an effort to find variations or mutations between the two, which may represent a cancer-driver. In some cases, researchers can then explore treatment options that might block that driver.

POG would not exist without the support of BC Cancer Foundation donors, who have been the primary funders for this program since it launched in 2012.

The interdisciplinary POG team (led by Drs. Janessa Laskin and Marco Marra) is committed to sequencing the genetic code of deadly metastatic cancers to pinpoint precise treatment options for individual patients. Through the POG program, a patient’s whole genome (about 20,000 genes) is sequenced.

Personalized Onco-Genomics explained

Within human cells are chromosomes that carry DNA. That DNA is organized into smaller units called genes. Genes hold instructions about how a cell should function, which affect a person’s various traits, such as eye colour. A complete set of genes is called a genome.

Each person’s genome carries unique variations (or mutations) that may or may not be harmful. Some of these mutations have been passed down through generations of the same family. Cancer is an example of a gene mutation that can be harmful. Mutations in tumour suppressor genes can cause genes to grow out of control, which may result in a mass or tumour. Examples of tumour suppressor genes include BRCA1 and BRCA2. Mutations in these genes can cause an increase in hereditary risk for certain types of cancer, including breast and ovarian.

Proof that genomics can change the way cancer is treated

Led by Drs. Marco Marra and Janessa Laskin at the BC Cancer Agency, phase 1 of the POG project started in July 2012 with 30 patients for whom standard treatment options had been exhausted. Each patient had three specimens sequenced: a fresh tumour biopsy, an archived tumour specimen, and blood for normal DNA.

From phase 1, researchers learned that the genomic structure of tumours changes over time, which explained why specific treatments can be effective for one type of cancer but not for another. The second phase of POG, which started in 2014 and accepted 300 patients, built on what was learned in the first phase of the trial.

As of September 2017, more than 900 participants were enrolled in POG. Of those enrolled, 569 have had sample collection and sequencing, and 524 of those have had analysis and reporting. Fifty cancer types have been explored so far, and of the cases completed to date 79 per cent yielded results that were deemed actionable by the POG team, meaning the data offered information that could be used in planning treatment. Results from POG have proven that genomics can fundamentally change the way cancer is treated.

Langley resident Zuri Scrivens began her cancer journey in 2011 when she was diagnosed with breast cancer 10 months after giving birth to her first child. Her story was featured on the recent CBC Nature of Things documentary called Cracking Cancer, which aired in February 2017. While initial treatments appeared to work, Zuri’s metastatic breast cancer quickly returned, spreading to her liver and lymph nodes.

She was then enrolled in POG and genomic analysis identified the fact that her cancer was driven by a mutation involving an insulin-like high-growth factor that was stimulating the cancer cells. The POG team scoured research, data, and discoveries to find a drug that might block that particular growth factor. They found it in a drug commonly used to treat diabetes. Zuri began taking that drug, along with standard hormone treatment, and responded well to the new protocol. Four months later, her cancer was undetectable.

Zuri’s response to the unconventional treatment is now being studied by experts to determine how many more patients might benefit from a similar approach. She is among a small percentage of participants known as “super responders” because their treatment was so successful.

Current cancer treatment is based on the type of cancer someone has so, for example, colon cancer is treated with drugs designed for colon cancer. But that approach doesn’t consider that people with the same type of cancer may have tumours that act differently and respond to different treatments.

That was the case for Vancouver resident Trish Keating, who was diagnosed with colon cancer in 2010. After surgery, chemotherapy and radiation treatment, she was told in 2013 when her cancer returned that it was terminal. Keating was enrolled in the POG program and the team discovered her cancer was driven by a specific protein. They then identified and administered an existing blood pressure medication that is known to block pathways to that protein. The results were rapid and dramatic. Eight weeks after starting her new treatment, Trish was tumour-free.

While their results are not typical of most participants and the long-term effects of these experimental treatments remain unknown, POG gave both Zuri and Trish hope for the future and valuable time with their families and friends.

“Treatment is getting better and the research we are all involved with is a driving force of change."

- Dr. Janessa Laskin, BC Cancer medical oncologist and senior scientist

First-of-its-kind trial aims for broader applications

Earlier this year, BC Cancer’s Dr. Dean Regier received a Strategic Priority Fund Award to explore the patient and economic impacts of POG-guided cancer treatment. To achieve this, Dr. Regier and his colleagues will consult with POG participants about the value they attach to genomic knowledge and its health outcomes. This information will help inform the cost-effectiveness of a POG approach versus the current standard of care.

Cancer is a disease of the genome. The POG program aims to sequence the genetic code of deadly metastatic cancers to pinpoint precise treatment options specific to individuals. 

The BC Cancer Agency’s POG project is the first program of its kind in the world and has been primarily funded by generous donations to the BC Cancer Foundation. Researchers believe the clues hidden in the cancer cells of program participants currently being examined will ultimately contribute to new individualized and effective treatment options that will benefit many more people with all types of cancer.

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