Saturday, April 12, 2014

Dogs Teaching Us a Thing or Two About Cancer Biology

The German shepherd standing on my front lawn, and his friends in the neighborhood, the rottweiler, the maltese, the shih tzus, the husky, and the other exotic breeds, have one thing in common: Like humans, they are living into their golden ages, and are increasingly showing up with diseases of old age, including cancer. Dogs once past the age of 10 years have a 50% chance of developing any type of cancer. (A 10 year old dog, depending on the breed, is same age as a 55-65 year old man.) 

All types of cancers seen in humans also show up in dogs. For example, take breast cancer: Like women, female dogs (those not neutered, or are at a breeder) also come down with breast cancer, generally called mammary cancer in dogs.

Further, not only the biology of cancer is similar in dogs and man, the dogs also respond to same cancer drugs that are used for humans.

Comparative Oncology

On March 31st, 2014, The New York Times profiled the Penn Vet Shelter Canine Mammary Tumor Program on its website. This innovative program, run by Dr Karin Sorenimo, the Professor of Oncology at the University of Pennsylvania, takes in shelter dogs for cancer treatment and care; the dogs in turn help advance research into the biology of cancer by ways that are impossible to do in humans.

Dogs typically have 10 mammary glands, and they often develop multiple tumors of various sizes and in development stages. The development stages can range from benign to cancerous (or malignant.)

By comparing the molecular profile of these breast cancer tumors which are at various stages of development, but all with same genetic background, researchers can ask specific questions, such as:

  • What are the switches (or signaling pathway changes) that occur when cancer advances from benign to malignant stage
  • What are the specific biomarkers for various stages of cancer
  • Can those biomarkers be used for targeted therapies in clinic (for humans) or in development
  • Or, can these biomarkers be used to try out therapies in dogs first before going to humans

NIH-NCI Comparative Oncology Program

Ten years ago, in 2003, the National Cancer Institute's Center of for Cancer Research (CCR) launched the Comparative Oncology Program (COP).

The purpose of this program was: 

  • to understand the biology of cancer
  • to promote clinical research on novel therapies for humans by treating pets (dogs and cats) with naturally-occurring cancers, and 
  • to bring innovative therapies to veterinary care

The clinical trials sponsored by the NCI's comparative oncology program are listed here.

Why so much much effort and tax-payer dollars have gone into comparative oncology program can be summed up by Dr Chand Khanna's statement to New York Times: “Every cancer that develops in a dog develops in a human, and for the most part, the reverse is true as well.” 

Therefore, what we learn by treating man's best friend can ultimately help humans themselves.

Dr. Chand Khanna developed the comparative oncology program at the National Cancer Institute’s Center for Cancer Research.

Canine Genetics

Different breeds of dogs are predisposed to different types of cancers. For example, Belgian shepherd are more likely to get gastric carcinoma, whereas prostate cancers are more common in Doberman pinscher. One of the reasons for high rate of cancer and predispositon to certain cancer type in different dog breeds is the loss of genetic diversity in these breeds.

The domestication of wild wolves and breeding of specific dog breeds while helping man create beautiful and prized canine friends, has also led to a loss of up to 35% of genetic diversity in pet dogs compared to their ancestors, the wild wolves. 

Nonetheless, the molecular analysis of tumors from these dog breeds has created an opportunity for researchers to investigate signaling pathways involved in tumor progression by providing multiple samples often from the same animal.

Dr Olga Troyanskaya, the Professor of bioinformatics at Princeton, is collaborating with Dr Sorenimo of UPenn, the chief oncologist of the shelter dog cancer program (Penn Vet mammary tumor program) to delineate cancer pathways in breast cancer.

Below are the similarities between dog and human breast cancer pathways (Source: Dobson JM. ISRN Veterinary Science, 2013, Article ID 941275)

Human breast cancerCanine mammary tumor

Gene sets/signaling pathways
 Wnt*b cateninUpregulationUpregulation
 MAPK cascadeUpregulationUpregulation

Beyond Breast Cancer

About 12 million American homes experience the anguish of their pets coming down with cancer every year, that's 6 million dogs and similar number of cats. These four-legged companions come down with all kinds of cancers as in humans. By promoting the research and cancer drug development for dogs, the NIH and other programs help both the pet owners as well as help understand human cancer.



Paoloni M, Webb C, Mazcko C, Cherba D, Hendricks W, Lana S, Ehrhart EJ, Charles B, Fehling H, Kumar L, Vail D, Henson M, Childress M, Kitchell B, Kingsley C, Kim S, Neff M, Davis B, Khanna C, & Trent J (2014). Prospective Molecular Profiling of Canine Cancers Provides a Clinically Relevant Comparative Model for Evaluating Personalized Medicine (PMed) Trials. PloS One, 9 (3) PMID: 24637659

Dobson JM (2013). Breed-predispositions to cancer in pedigree dogs. ISRN Veterinary Science, 2013 PMID: 23738139

1 comment:

  1. cancer is a word we all loathe to hear. Unfortunately, it is a very real situation that we encounter not only with people, but also with our pets. While not a lot of people are knowledgeable about dog cancer, studies are underway to help us find effective methods on how to better deal with this disease.

    Around half of all reported cases of canine cancer are of the skin, twenty percent are of the mammary glands, and the others are of the lymphatic, alimentary, reproductive, etc. Cure for the animal varies depending on his specifics like breed, age, weight, and other health related concerns. Listed here are some alternative cancer treatments for dog that will guide you in making the best decision for your pet.

    Cancers are generally defined by a growth of an abnormal tumor in a particular area of the animal. As you may have already known, there are two kinds of tumors: benign and malignant. Benign tumors are growths that have clear edges. As such, these tumors can be fairly easily removed through surgery. Malignant tumors have no defined edges and usually spread; therefore taking it out entirely through means of surgery is a lot more difficult, if not impossible.

    Radiotherapy is the treatment wherein radiation is used to destroy the cancer cells in damaged tissues so they will not reproduce. The challenge is to give the correct dosage so that the radiation will only affect the cancer cells and not harm the normal cells. To manage this, radiation is given in lower quantities at regular intervals. This will ensure that the cancer cells are dealt with while the normal cells are allowed to recover effectively.

    Unlike when done with people, radiation does not give the dog harmful side effects like nausea and vomiting; primarily because of the smaller quantity used. It is estimated to prolong the life of the animal for months instead of just weeks as previously believed. Hyperthermia, another treatment done to kill cancer cells through the employment of high temperature, is used alongside radiation.

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