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. What our study showed is that if we can capture the genomic and treatment data for these dogs, it can help us quickly home in on the most promising new applications of existing drugs for human cancer patients by extending the FDA-approved drug label. If we could collect and analyze data from all the canine cancer patients being treated in America’s 30,000 vet clinics, we could essentially run a continuous and massive “clinical study” using real patients in real world settings.

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 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.

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• Source: https://www.statnews.com/2023/06/16/dog-cancer-dna-human-treatment-clinical-trials/?utm_campaign=rss