A conversation with leading Canadian oncologist Dr. Janessa Laskin
Personalized OncoGenomics, probing an individual’s genome for bespoke cancer treatment, is a reality for a select group of patients with incurable cancer in British Columbia. The project, known as POG, now in its seventh year and offered through BC Cancer, has vaulted its clinical leader, Dr. Janessa Laskin, into the forefront of international discussion on the future of this revolutionary approach to cancer.
A medical oncologist at BC Cancer, Vancouver, Dr. Laskin has drawn at least four conclusions from her ground-breaking work with POG, a novel collaborative research project between clinical oncologists and the Michael Smith Genome Sciences Centre in Vancouver:
• Cancer is a disease of the genome
• Genomic technology can help us better understand cancer biology, behaviour and response to therapy
• Genome/transcriptome data can be used to identify novel treatment strategies
• Such comprehensive data can make a difference in clinical care for the individual and this knowledge can be translated to help patients on a global scale
POG is the only project of its kind to accept adult and pediatric patients with all types of advanced cancer for evaluation in such extensive detail. As of August 2019, 1,068 patients have been enrolled in the study since the program’s launch. Whole-genome and RNA sequencing is done on biopsied cancer cells taken from every patient, generating enormous amounts of data which are then subjected to thorough analysis and discussion by researchers and clinicians. Their combined effort is focused on generating hypotheses about what might be driving a particular person’s cancer to grow uncontrollably and to exploit those vulnerabilities with drug treatments. Of the cases completed, over 80 per cent of the time the genomic/transcriptomic data generated potentially clinically actionable drug targets that could often be aligned to actual treatments for the individual patient.
POG considers cancer a disease of genetic mutations with drivers that are individual to the persons affected. Using a patient’s analyzed genomic and transcriptomic (RNA) data, POG can search for drug treatments – some of which may be off label or approved for other diseases – with potential to contain or neutralize the drivers.
Conventionally, cancer has been approached as a disease differentiated by its site of origin and it has been treated according to standards, based on what has helped others affected in the same way. In some respects, it has been a one-size-fits-all approach.
“Unfortunately,” Dr. Laskin has acknowledged, “we know that this strategy can only help some patients, which means that many people endure potentially toxic and ineffective treatments. POG is about trying to identify the right treatment for the right person at the right time; we are still in the discovery phase but POG has had its share of fascinating success stories as well as disappointments, as outlined in a 2017 episode of The Nature of Things, broadcast by CBC.”
Yet even at this early trial stage, the concept behind POG is considered promising enough that many observers in the cancer field expect it to eventually provide more options to patients, for whom the traditional approach has been unsuccessful, and to present scientists and clinicians with new, fruitful lines of inquiry for more effective cancer treatments.
Dr. Laskin stopped at Genome Atlantic on a visit sponsored by Sanofi-Genzyme, Genome Atlantic, Integrated Microbiome, Illumina and Dalhousie University. She was in Halifax to speak to the local medical and research cancer community about POG. To mark the visit, we asked her five questions:
Do you find oncologists and cancer researchers open to the idea that cancer is a disease of the genome or do they need convincing?
At this point I think there is a general agreement that the unregulated cell growth that defines cancer is driven by something wrong at the genome or transcriptome level. We have clear examples of success when we are able to identify and target these specific abnormalities and many of these are now integrated into the standard of care for testing and treating certain types of cancers. Lung cancer with EGFR mutations, melanoma with BRAF mutations would be examples of this integration of genomic technology directly into mainstream care. However, it is also clear to clinicians and researchers that this is still a wide-open space and there are many aspects that are as yet unclear and many of these likely lie in the space around the genome such as epigenetics, proteomics, and so on.
It has been found that chemotherapy changes the genome. Is this conclusion an obstacle or an opportunity for improved cancer based on the POG approach?
We have a lot to learn about the untreated cancer genome, so the changes after chemo- or radiation therapy pose an additional important challenge. We have demonstrated many of these changes over time with serial biopsies and analyses; this is one of the most interesting aspects of the research aspect of POG. In the future I am hopeful that we can learn how to harness the power of this sort of knowledge; by understanding how a cancer might evolve in the face of a specific treatment perhaps we can guide it in a direction that would allow a treatment we could anticipate and therefore take advantage of.
Apart from cases of remission, how does POG know if it has improved the condition of its patients, given that all the participants have been diagnosed with terminal cancer. In other words, how does POG evaluate success?
This is an important question that everyone in the “precision” medicine field is grappling with; if you are treating each individual how do you know they would not have done just as well with a standard or different therapy? There have been many approaches to this in clinical trials, comparing how a person did on the previous treatment is the most common method. For POG we have been more focused on development of a process to create meaningful analyses and testable hypotheses so we have not yet focused on this sort of clinical value.
We do have some early data with matching cohorts of patients who have not had treatment informed by POG and we do find that patients treated based on POG information do at least as well if not better; but these are early days and the study was not designed to answer that specific question. It is definitely something we are motivated to address, and we work closely with our Health Economics team to try to measure and understand the value of this sort of data. And “value” can mean many things, not just financial but also the utility of having more information and a biological rationale to choose treatments.
We do think that in time finding the right treatment for each person will be more effective care, though it may not be less expensive. If people are living longer, they will need to be on treatment for longer.
The POG project has been running for seven years now. Has the program provided enough proof of concept yet, to be considered worthy for adoption into the health care system? If not, what stands in the way?
POG has been an innovation and discovery project, we would not envision that POG as it currently exists would be the right answer for every person with cancer. It is clear that more information is helpful for treatment planning and to understand cancer biology and evolution. Once we have sequenced tens or hundreds of thousands of these individual cases, I think we will have a much better idea of what sort of patient requires each level of testing. And as we acquire this experience, the technology will change, and we need to adapt along with it.
Much as you might not have envisioned a smart phone when you bought your first cell phone, your needs changed as the technology evolved. For now, funding is a significant issue, we need to amass enough data to understand the best way to include genomic technology into care.
What is next for the POG project?
We have a number of exciting projects on the go. We are about to launch a trial using POG data to identify markers for immunotherapy. This is an area of great need because there are no reliable markers for these drugs currently, and they are costly and often toxic. We have been doing some innovative work in pancreas cancers, understanding that there are some niche populations in this devastating cancer that can be selected out by POG-like analysis.
Our next goal is to work close with the Marathon of Hope Cancer program in collaboration with the Terry Fox Research Institute, to bring cancer genomics to all Canadians. We have a novel program to generate information more rapidly for clinical use while selecting some genomes for more in-depth analysis. We are committed to collaborations and data sharing, and we hope to bring our experience into the field, to pave the way for other researchers and clinicians.
Genomics is the future, and the future is hope.