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The pace of genomic analysis of canine cancers has rapidly increased over the past decade. As we continue to integrate these data into clinical settings, it provides unprecedented opportunities to expand our diagnostic, prognostic and therapeutic toolbox.
In the sixth webinar of this series, we welcome Dr. Heather Gardner, DVM, DACVIM (Oncology), to discuss some of the scientific and logistical challenges in the genomic analysis of canine cancer during the global pandemic. Dr. Gardner highlights promising areas of research in veterinary oncology, and provides answers to some of your most asked questions.
Dr. Heather Gardner, DVM, DACVIM (Oncology)
Transcript of Conversation
What are the most important advancements in canine genetics over the past 5 years? There has been an explosion of data over the past 5 to 10 years. It’s been facilitated by two things:
- Technology Developments: The development of technology generates data. It gives us the ability to have tools to analyze and interpret data in a way that is relevant to the research and clinic setting.
- Building a Community: Coming together as a team to help breakdown individual silos that we sometimes find ourselves in. As a result, there is a better understanding of how we can position ourselves to address the limitations that still exist. We can figure out how to leverage our strengths, potentially to understand things relevant in particular breeds and systemic alterations as they evolve in the course of a disease.
What technology has advanced and allowed us to participate in the genomic revolution?
Next generation sequencing (NGS) has advanced and can be used as a launching pad for what we can do with genomic data. We can find ways to make it more accessible. There is a huge landscape of literature out there, like RNA sequencing data. Formulating a complete picture will help facilitate those advancements as we take our learnings and turn it into clinical tools.
Why do you think these are so important to clinicians and to the wider stakeholder community?
Targeted therapy relies on an understanding of how particular targets are regulated, including the molecular landscape of the disease. Beyond drugs, the information is very important from a diagnostic and prognostic standpoint. In a clinical setting, some tests are easy to perform. Yet, they yield a lot of information on how a treatment protocol is assembled for the patient.
Why are these technological advancements in genomics important to pet owners?
These technological advancements give options to pet owners. We’re always looking for ways to get better at what we’re doing, and the advancements give us a way to guide pet owners through the pros and cons of different treatment options. Clients are very passionate, and they want to be involved and empowered in their pet’s cancer journey. We want to enable them to participate. There is a desire to contribute in any way possible to further the understanding of the genetics of the disease. We have found that many want to turn the experience into something good for other people and other pets. In terms of the pandemic landscape, we need to look at how we can construct treatment plans and find what is feasible for the pet parent and animal. Understanding what is regulated in the tumor and expanding the toolbox provides them with more options.
When you analyze genomic data for canine tumors, what type of actionability would you expect and why? Why isn’t the actionability 100%?
This all speaks to the understanding we have of pathways and targeted therapies. Actionability depends on the tumor. The type of tumor dictates what we know at a genomic level, and the observable responses to genomic therapy can be quite dramatic.
There is a lot going on. We know about drugs and understand the aborations in tumors. We can argue that part of the reason a drug is working is due to a targeted effect we haven’t observed or yet understand. Similarly, in the context of the messy tumor, it is easy to understand how development of the new mutation that circumvents an important signaling pathway affects the outcome of the patient.
Compare and contrast tumor genomics in human pediatrics and veterinary oncology
In the context of an osteosarcoma publication, several features that stood out. Epigenetic alterations and alterations that impacted 40-50% of the population were evaluated. It was still a very heterogeneous and complex landscape In a lot of ways, it is reflective of pediatric tumors that we see. They tend to be structurally diverse.
To some extent, in an inbred population, we can leverage this information. Canine publications focus on specific breeds of dogs to help identify features to investigate further. The findings are a bit surprising, but this is because it’s a relatively homogenous population.
Has COVID-19 affected your research? If so,how?
There has been a dramatic effect on the clinical and benchtop research realm, especially since I cannot go into the lab. It requires rethinking of our approach to these problems as we consider how the new normal will look with COVID-19. It has completely changed how we are operating. It is amazing to see how the community has come together to work as a team for everyone’s benefit. There is a paradigm shift, but it is great to see how everyone is adapting in both settings.
Do you think COVID-19 will increase funding into genomic research over the next few years?
Many more local opportunities are available for everyone, especially for COVID-19 specific research. It will be interesting to see how this plays out in the long term and how the opportunities can incorporate more people.
What are you most excited about in terms of canine genetic research?The most exciting thing is there are currently opportunities that weren’t thought to be possible a decade ago, especially with clinics. Clinical trials and observing how it affects the patients is a powerful tool. The process helps us understand how we can optimize and best position ourselves to get genomic data. This puts us in a place that is beneficial for both veterinary and human medicine.
Collecting data is important, but equally important is for all of the datasets to be able to talk with each other. Can you talk about what initiatives are currently underway to help foster this goal in terms of canine genetic information? And in terms of comparative genomic information?
There are several components in leveraging the power of all the datasets. It brings in clinical data and puts it into the context of the genomic data that we’re gathering. Several efforts are underway to build institutions to facilitate multi institutional projects. For example NIH, ICDC, and COHA are making the information available.
- COHA/ CTSA - One Health Alliance: Access to large genomic canine datasets and modeling it off the human data
- ICDC - Integrated Canine Data Common: Large genomic canine datasets
There are initiatives on the human side, too! Count Me In helps to accelerate research on a variety of tumors.
These efforts leverage data we’re learning about in dogs to better understand comparative aspects and improve outcomes for both species
Genomic information and clinical information -- these are often done separately. Why is it important to obtain this information together? What makes it so powerful and vitally important?
Think about it in terms of the perspective of the tumor: at some point, we’re put in a situation where something isn’t working, and we are running out of options
The ability to correlate the tumor’s molecular and genomic changes over time, along with clinical changes gives a better understanding of actionability and how we should be thinking about these diseases in the future.
We talked a little about pathway dysregulation in cancers, can you talk about what that is?
These things go hand in hand. Pathway dysregulation refers to mutations or translocations that have turned on a specific gene, or signaling specific pathway is turned on. If we can figure out the pathways for resistance, we can use targeted therapies to address it.
Who are some of the other colleagues you’d like to collaborate with in the veterinary oncology field?There are lots of people on the basic research and clinical research side. It would be the most exciting thing to collaborate with them!
Do you think there is a role for tele-oncology during COVID19 pandemic?Regulations vary state-by-state COVID-19 pandemic. Based on the setting, there are many tools being incorporated. The way we’re communicating with owners now is different from how it was a few months ago. There are many ways to think about how to best position tele-oncology for patients, especially with restrictions in place.
How do we best identify the gene alterations for drivers, versus the ones that are not significant to the disease process? How do we best target our therapy?There are many ways to approach this in different settings, from the bench to small trials. Small trials help to find a signal. From there, we can figure out if we should put effort in and pursue further research.
We find so much and it can be very daunting. There are a lot of algorithms being developed. Is there anything specific that you use in terms of algorithms of significance in a finding?
It depends on what is being analyzed. With the genetic alterations, there are tools available to try to predict.
In terms of complex tumors, I ask, “How do I know if this is something that is sitting there, or can it be actionable?” It really requires me to step back to ask how I can test things in a clinical scenario or get more information from a functional standpoint.
There is no easy answer. We will always ask ourselves, “How do I know if this is something that can be relevant,” especially from a research standpoint.
How can people in private practice help accelerate research?
There are lots of ways! It goes back to the idea of working as a team and promoting teamwork to facilitate collaborative interactions.
Technological developments make this easier. Ongoing trials can be done in a private practice to collect follow-up data. There are lots of avenues for the interaction, but it all goes back to working as a team.
Can you comment on the concept of actionability with regard to the ability to target known mutations versus considering more immunogenic tumors (i.e. osteo or melanoma), and the ability to utilize immunotherapy as a type of targeted therapy. How do you prioritize working towards a therapy for anything defined as actionable?
There is rarely one thing to end the tumor. The focus becomes:
- How to integrate things into a larger therapeutic picture for the patient
- How to leverage specific features of the disease at any given time to give it the best possible outcomes for the patients
The end result will likely involve a combination of everything as a package, from immunotherapy, standard therapeutics, to targeted therapy. It’s all a package, and not necessarily one versus the other.
How much value is it to compare canine to human cancer mutations in terms of response to targeted therapies?This all goes back to the question of, “Which mutation is driving the disease? Do we think mutation A in a canine tumor is driving the disease? Is mutation A analogous in the human disease?” It helps us understand particular aspects of alterations.
When we look at large genomic datasets, we try to make connections by comparing information to see if the mutation is also detrimental on the human side. Sometimes, the answer is yes. For example, when examining osteosarcoma, we turned to the human cancer literature and found 15 tumors with a detrimental mutation. We figured it was something to follow up on in canines to see if the mutations did the same thing.
The COVID-19 pandemic is evolving quickly and you need to find information at the appropriate depth and credibility level. To that end we have started a webinar series to address the academic and practical aspects of the COVID-19 crisis as they pertain to the veterinary world.
The webinar format includes a segment with an expert on a specific aspect and a segment with 1-3 practicing veterinarians reporting from the field.
If you would like to get our webinar invites, please send us a note using our veterinarian contact us form.