This year, nearly 6 million dogs in the U.S. will receive a cancer diagnosis. That’s approximately
three times greater than the number of Americans who will be diagnosed with cancer this year,
even though humans are estimated to outnumber pet dogs by nearly 4 to 1. Yet the genetic similarities between human and dog cancers may point the way to treatments that can save lives on both ends of the leash.
Most of the dogs that develop cancer this year won’t receive any treatment for their disease.
Those that do will mostly be put on a chemotherapy regimen, a one-size-fits-all treatment that
does little to arrest the unrelenting march of their deadly illness.
It doesn’t have to be this way. For years, scientists have known that dogs respond well to cancer
treatments that target specific mutations in their tumors. The reason is that dog and human
cancers have a lot in common — they are genetically homologous, occur naturally at similar
rates, and respond to the same treatments. Dogs are, in other words, about as perfect a model
of human cancers that we could hope for. But until recently they have been an untapped
resource in our fight against cancer.
In 2019, One Health — a company one of us, Christina, founded and runs as CEO, and where
James is AI architect — began building what has become the world’s largest dog cancer
clinico-genomic dataset, which is unique not just for its size but the quality of information it
contains. Over the course of the past three years, we have collected genomic data from the
tumors of more than 4,000 dogs being treated for cancer at 900 vet clinics across the country.
Earlier this year, we published data on a subset of 1,100 dogs in a study in Nature Precision
Oncology. Each of the dogs in the paper — and in the full dataset, which adds new dogs every
week — is somebody’s pet, and one of our goals was to help identify the most promising
treatments for each beloved family member. To make it happen, we use One Health’s FidoCure
platform to sequence the tumor DNA of every dog in our data set, enable access to treatments
via a pharmacy partner, record their treatment, and monitor their outcome.
When we analyzed the data, we were astounded by what we found. Hidden among the
constellation of more than 1.2 billion data points in our canine cancer database was an
unmistakable pattern that revealed just how closely the canine human cancer journey mirrors
our own. Dog patients develop the same types of cancers as humans at remarkably similar
rates, they respond to the same cancer drugs, and they have the same prognosis. Oncologists
have known that dogs are a great model of human cancers for decades, but they mostly
focused on isolated similarities, such as the analogous structure of dog and human cancer cells.
Our data suggests that the canine cancer patient’s journey — from diagnosis to treatment to
outcome — is nearly identical to the human cancer journey.
But there was an even bigger surprise lurking in our data. By using data science and AI, we
were able to identify a cohort of canine cancer patients that had received “off-label” cancer
drugs and saw a remarkable increase in their median survival times — in some cases extending
their expected lifespans by a factor of three. This was remarkable because all of these pet
patients were receiving small molecule cancer drugs, a type of therapy that is paired with
specific genetic mutations found in tumors. These small molecule drugs were originally
designed for human patients, but because dog and human cancers are so similar our canine
companions can benefit from them, too.
There’s an important difference in treating canine cancer patients with small molecule drugs,
however. Whereas the drugs that oncologists can prescribe a human cancer patient are
generally restricted by the drug’s FDA-approved label to the type of cancer they have, vet
oncologists aren’t similarly limited to such rigorous “quality of care” standards. Vets can — and
do — prescribe the treatment they think will be most effective for their patients in consultation
with pet parents. For example, there is some evidence that dasatinib, which is used to treat a
type of leukemia that exhibits T315I mutations, may also be effective at treating cancers with
BRCA mutations, which is typically associated with breast cancer. For humans, however,
dasatinib is available only to treat leukemia. But if a vet is treating a canine patient with breast
cancer, they may decide to use dasatinib if other treatments aren’t working or are unavailable
because canine patients aren’t bound by the same legal restrictions on treatments as humans.
An individual vet might prescribe an “extra-label” small-molecule drug to a dog with a specific
type of tumor mutation only a few times a year. But this is happening dozens, if not hundreds of
times for this tumor type across all veterinary clinics.
The relative freedom of a veterinarian to choose the types of therapies their pet patients receive
presents an enormous opportunity to accelerate the development of cancer drugs. Today, the
way that human cancer drugs are discovered is mostly through trial-and-error and relies heavily
on testing new drug candidates in mice, which leave a lot to be desired as cancer models.
Bringing a new human cancer drug to market is a lengthy and expensive process that can take
upwards of a decade and cost billions of dollars. And by one estimate, 97% of new cancer drug
candidates fail out of clinical trials well before they ever make it to market. That’s a lot of time,
energy, and resources we can’t afford to waste in our fight against cancer.
What our study suggested, however, is that by providing canine cancer patients with existing
cancer drugs and carefully tracking their genetic profiles and outcomes, it’s possible to identify
novel uses of existing drugs and the most promising cancer drug candidates for a human trial.
Rather than the current drug development paradigm of searching for a needle in a haystack, our
approach brushes the haystack aside to reveal the needle. Using only a relatively small cohort
of 1,000 dogs and 10 small molecule-drugs, we were already able to identify promising new
treatment applications for two of those existing drugs. By using this data, oncologists can
fast-track these drugs for human clinical trials and, if those trials are successful, get these drugs
into the bodies of human cancer patients who need them — all in record time.
Pharmaceutical companies are starting to pay attention to this new drug development paradigm.
One of the first to recognize the potential of canine cancer patient data was Eisai, a Japanese
pharmaceutical company that used our platform to launch a study to see whether one of their
existing cancer treatments, a drug called eribulin used to treat breast cancer and liposarcoma,
might also be effective in treating angiosarcoma. Buoyed by the promising results of our
collaborative study, Eisai was able to quickly launch a human clinical trial, which is now in Phase
II only three years after we published our initial results.
Comparative oncology — the study of canine cancer patients as models of human cancer — is
a burgeoning area of research that has attracted increasing research interest and federal
funding. In 2017, the National Cancer Institute awarded $11.5 million in grants to six veterinary
schools to study cancer immunotherapies in pet dogs, which has already led to two Phase 1
clinical trials in humans led by researchers at the University of Minnesota and the University of
Colorado. In 2022, the NCI expanded its comparative oncology program to six other veterinary
schools. We’re optimistic that this program will continue to produce important new discoveries
about both human and dog cancers.
One Health isn’t the only company working on bridging the gap between canine and human
oncology. For starters, the blockbuster human cancer drug Imbruvica was helped by a clinical
trial in pet dogs with cancer run at Colorado State Vet School. Over the past few years, a
growing number of startups have pioneered incredible new ways to leverage precision
diagnostic and treatment techniques from human oncology to advance the treatment of pet
cancer patients. ImpriMed, for example, is focused on personalized treatment selection starting
with the pets and moving to humans. Meanwhile, a company called Anivive has repurposed a
human cancer drug for canine cancer and Basepaws is building a unique database for cat
cancer patients.
But most comparative oncology work on canine cancer patients involve relatively limited clinical
trials, which limits their effectiveness in advancing precision cancer treatments for dogs and
humans. To make that happen, we need a lot more data — and the best way to get it is by
bringing the research to canine cancer patients.
Today, most veterinary clinics aren’t collecting the vital genomic data on canine cancer patients
that is needed to provide the most effective care for their patients and drive new insights on
effective therapies. The reason for this is that until recently collecting genomic data and
analyzing it with machine learning systems was prohibitively expensive for veterinarians. But as
the cost of genetic sequencing and big data analysis continues to plummet, we can no longer
afford to ignore this vital tool in our fight against cancer.
Pet owners needn’t be concerned that they’re footing the bill for drug development at major
pharmaceutical companies or turning their pets into research subjects, either. If a pharma
company wants to enroll canine patients in a clinical trial using the FidoCure platform, the
company pays the full cost of the trial just as it would in a human trial. It’s up to dog owners to
decide if they want to enroll their pet.
Our dogs are our best friends in sickness and in health, and by making potent new treatments
available to canine cancer patients, collecting their genomic data, and monitoring their outcome
we can usher in a new paradigm of cancer drug development that has the potential to save
millions of lives on both ends of the leash.
Christina Lopes is CEO of One Health. James Zou is a professor at Stanford University.
Read the Original:
https://www.statnews.com/2023/06/16/dog-cancer-dna-human-treatment-clinical-trials/
