Comparative oncology

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Comparative oncology integrates the study of oncology in non-human animals into more general studies of cancer biology and therapy. The field encompasses naturally seen cancers in veterinary patients [1] and the extremely low rates of cancers seen in large mammals such as elephants and whales. [2]

Contents

Mammalian cancers

Species that are treated in the veterinary clinic, including dogs, cats, horses and ferrets, present human-relevant cancers. [1]

Canines

Of these, the dog has the greatest number of incidents. [1] One in four dogs older than 2 dies of cancer, a rate that has increased, which may in part be explained by reductions in other causes of death. Canine cancer shares features with human cancer, including histology, tumor genetics, molecular targets, biological behavior and therapeutic response. Canine histologies include osteosarcoma, melanoma, non-Hodgkin's lymphoma, leukemia, prostate, breast and lung cancer, head and neck cancer, soft tissue sarcomas and bladder cancer. Tumor initiation and progression are influenced by age, nutrition, sex, reproduction and environmental exposure. Canine models support the study of metastasis, disease recurrence and resistance patterns, with relevance to human cancers. [1]

Since 2009 some ten drugs have been developed in part based on studies with dogs. On July 3, 2019 FDA approved selinexor (Xpovio) for multiple myeloma patients who have failed five or more therapies. Verdinexor is the veterinary form of this drug. [3] It is under study for canine lymphoma and as a human antiviral therapy. [4]

Large mammals

Since cancer typically begins as a mutation in a single cell, risks should increase with the number of cells in an organism. Elephants carry 100 times as many cells as humans, while whales have ten times more than elephants. Both should experience higher cancer rates than humans. However, these species instead have few cancers. This situation is known as Peto's paradox. [5]

Around 50 MYA, mammals began living in the sea, later evolving into whales. They remained small until about 3 MYA when they reached sizes common to modern cetaceans. As whale sizes increased, tumour-suppressor genes increased in number and effect. [2]

33 tumour-suppressing genes have been identified in humpback whales. These include atr, which detects damage to DNA and halts cell division; amer1, which slows cell growth; and reck, which limits metastasis. Humpbacks have multiple copies of genes that promote apoptosis. Gigantism in cetacea is associated with selective pressure in favor of tumor-suppressing genes. [2]

Cancer biologists are familiar with the atr, amer1 and reck genes because they are found in humans. Whales may also harbour tumour-fighting genes unknown in humans. [2]

Elephants have a cancer-mortality rate of about 5% (humans face 11–25%). Elephant genomes include tp53, a gene that encodes apoptosis-inducing protein p53. Humans have two copies of tp53—one from each parent. If one copy is dysfunctional humans experience Li-Fraumeni syndrome, accompanied by cancer. By contrast, elephant chromosomes have 40 copies of tp53. [2]

Elephant p53 appears to be more powerful than its human counterpart. One experiment involves lipid spheres loaded with proteins, including a synthetic form of elephant p53. [2]

Other species

Researchers are investigating cancer rates in 13,000 animal species, including 170,000+ specimens, including sponges that have no reported cancer. [2]

Tumour-suppressing genes have been identified in 65 species of mammal. Naked mole rats experience low cancer rates even though they are smaller than humans. Crocodiles and birds also experience low cancer rates. Birds may have inherited their resistance from their much larger dinosaur ancestors. [2]

Related Research Articles

Experimental cancer treatments are mainstream medical therapies intended to treat cancer by improving on, supplementing or replacing conventional methods. However, researchers are still trying to determine whether these treatments are safe and effective treatments. Experimental cancer treatments are normally available only to people who participate in formal research programs, which are called clinical trials. Occasionally, a seriously ill person may be able to access an experimental drug through an expanded access program. Some of the treatments have regulatory approval for treating other conditions. Health insurance and publicly funded health care programs normally refuse to pay for experimental cancer treatments.

p53 Mammalian protein found in Homo sapiens

p53, also known as Tumor protein P53, cellular tumor antigen p53, or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins are crucial in vertebrates, where they prevent cancer formation. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence TP53 is classified as a tumor suppressor gene.

<span class="mw-page-title-main">Tumor suppressor gene</span> Gene that inhibits expression of the tumorigenic phenotype

A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes.

<span class="mw-page-title-main">Osteosarcoma</span> Cancerous tumour in a bone

An osteosarcoma (OS) or osteogenic sarcoma (OGS) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin and that exhibits osteoblastic differentiation and produces malignant osteoid.

<span class="mw-page-title-main">Burkitt lymphoma</span> Cancer of the lymphatic system

Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. It is a highly aggressive form of cancer which often, but not always, manifests after a person develops acquired immunodeficiency from infection with Epstein-Barr Virus or Human Immunodeficiency Virus (HIV).

<span class="mw-page-title-main">Li–Fraumeni syndrome</span> Autosomal dominant cancer syndrome

Li–Fraumeni syndrome is a rare, autosomal dominant, hereditary disorder that predisposes carriers to cancer development. It was named after two American physicians, Frederick Pei Li and Joseph F. Fraumeni Jr., who first recognized the syndrome after reviewing the medical records and death certificates of 648 childhood rhabdomyosarcoma patients. This syndrome is also known as the sarcoma, breast, leukaemia and adrenal gland (SBLA) syndrome.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

<span class="mw-page-title-main">Canine transmissible venereal tumor</span> Histiocytic tumor of the external genitalia of the dog and other canines

A canine transmissible venereal tumor (CTVT), also known as a transmissible venereal tumor (TVT), canine transmissible venereal sarcoma (CTVS), sticker tumor and infectious sarcoma, is a histiocytic tumor of the external genitalia of the dog and other canines, and is transmitted from animal to animal during mating. It is one of only three known transmissible cancers in mammals; the others are devil facial tumor disease, a cancer which occurs in Tasmanian devils, and contagious reticulum cell sarcoma of the Syrian hamster.

Epilepsy in animals is a group of neurological disorders characterized by seizures, caused by uncontrolled, abnormal bursts of electrical activity in the brain. They can start and stop very abruptly and last any amount of time from a few seconds to a few minutes. Canine epilepsy is often genetic but epilepsy in cats and other pets is rarer, likely because there is no hereditary component to epilepsy in these animals.

<span class="mw-page-title-main">Lymphoma in animals</span> Type of cancer in animals

Lymphoma (lymphosarcoma) in animals is a type of cancer defined by a proliferation of malignant lymphocytes within solid organs such as the lymph nodes, bone marrow, liver and spleen. The disease also may occur in the eye, skin, and gastrointestinal tract.

<span class="mw-page-title-main">Histiocytoma (dog)</span> Benign tumor in dogs

A histiocytoma in the dog is a benign tumor. It is an abnormal growth in the skin of histiocytes (histiocytosis), a cell that is part of the immune system. A similar disease in humans, Hashimoto-Pritzker disease, is also a Langerhans cell histiocytosis. Dog breeds that may be more at risk for this tumor include Bulldogs, American Pit Bull Terriers, American Staffordshire Terriers, Scottish Terriers, Greyhounds, Boxers, and Boston Terriers. They also rarely occur in goats and cattle.

<span class="mw-page-title-main">Veterinary oncology</span>

Veterinary oncology is a subspecialty of veterinary medicine that deals with cancer diagnosis and treatment in animals. Cancer is a major cause of death in pet animals. In one study, 45% of the dogs that reached 10 years of age or older died of cancer.

<span class="mw-page-title-main">Cancer in dogs</span>

Cancer is the leading cause of death in dogs. It is estimated that 1 in 3 domestic dogs will develop cancer, which is the same incidence of cancer among humans. Dogs can develop a variety of cancers and most are very similar to those found in humans. Dogs can develop carcinomas of epithelial cells and organs, sarcomas of connective tissues and bones, and lymphomas or leukemias of the circulatory system. Selective breeding of dogs has led certain pure-bred breeds to be at high-risk for specific kinds of cancer.

Many types of skin tumors, both benign (noncancerous) and malignant (cancerous), exist in cats and dogs. Approximately 20–40% of primary skin tumors are malignant in dogs and 50–65% are malignant in cats. Not all forms of skin cancer in cats and dogs are caused by sun exposure, but it can happen occasionally. On dogs, the nose and pads of the feet contain sensitive skin and no fur to protect from the sun. Also, cats and dogs with thin or light-colored coats are at a higher risk of sun damage over their entire bodies.

<span class="mw-page-title-main">Aggressive lymphoma</span> Medical condition

Aggressive lymphoma, also known as high-grade lymphoma, is a group of fast growing non-Hodgkin lymphoma.

<span class="mw-page-title-main">CDKN2A</span> Protein-coding gene in the species Homo sapiens

CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. It is ubiquitously expressed in many tissues and cell types. The gene codes for two proteins, including the INK4 family member p16 and p14arf. Both act as tumor suppressors by regulating the cell cycle. p16 inhibits cyclin dependent kinases 4 and 6 and thereby activates the retinoblastoma (Rb) family of proteins, which block traversal from G1 to S-phase. p14ARF activates the p53 tumor suppressor. Somatic mutations of CDKN2A are common in the majority of human cancers, with estimates that CDKN2A is the second most commonly inactivated gene in cancer after p53. Germline mutations of CDKN2A are associated with familial melanoma, glioblastoma and pancreatic cancer. The CDKN2A gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

Gendicine is a gene therapy medication used to treat patients with head and neck squamous cell carcinoma linked to mutations in the TP53 gene. It consists of recombinant adenovirus engineered to code for p53 protein (rAd-p53) and is manufactured by Shenzhen SiBiono GeneTech.

Peto's paradox is the observation that, at the species level, the incidence of cancer does not appear to correlate with the number of cells in an organism. For example, the incidence of cancer in humans is much higher than the incidence of cancer in whales, despite whales having more cells than humans. If the probability of carcinogenesis were constant across cells, one would expect whales to have a higher incidence of cancer than humans. Peto's paradox is named after English statistician and epidemiologist Richard Peto, who first observed the connection.

Laura Attardi is the Catharine and Howard Avery Professor of the school of medicine, and professor of radiation oncology and genetics at Stanford University where she leads the Attardi Laboratory. Attardi studies the tumor suppressor protein p53 and the gene that encodes it, TP53, to better understand mechanisms for preventing cancer.

<span class="mw-page-title-main">Mastocytoma in dogs</span> Mastocytoma in dogs is a neoplasm

Mastocytoma in dogs is a neoplasm (neoplasia) originating from mast cells in the domestic dog, which occurs mainly in the skin and subcutis. Mastocytoma are not only extremely common in dogs, but also tend to be much more malignant in them than in other animal species. The average survival time for malignant tumors is only four months, whereas for benign tumors it is over two years.

References

  1. 1 2 3 4 Paoloni, Melissa C.; Khanna, Chand (November 2007). "Comparative Oncology Today". Veterinary Clinics of North America: Small Animal Practice. 37 (6): 1023–1032. doi:10.1016/j.cvsm.2007.08.003. PMC   2174910 . PMID   17950880.
  2. 1 2 3 4 5 6 7 8 "In fighting cancer, look to what other animals do". The Economist. 2019-06-29. pp. 75–76. ISSN   0013-0613 . Retrieved 2019-07-01.
  3. "FDA Conditionally Approves First Oral Tablet to Treat Lymphoma in Dogs". FDA.
  4. Marill, Michele Cohen (2019-07-12). "Why Dogs Now Play a Big Role in Human Cancer Research". Wired. ISSN   1059-1028 . Retrieved 2019-07-14.
  5. Tollis, Marc; Robbins, Jooke; Webb, Andrew E; Kuderna, Lukas F K; Caulin, Aleah F; Garcia, Jacinda D; Bèrubè, Martine; Pourmand, Nader; Marques-Bonet, Tomas (2019-05-09). "Return to the Sea, Get Huge, Beat Cancer: An Analysis of Cetacean Genomes Including an Assembly for the Humpback Whale (Megaptera novaeangliae)". Molecular Biology and Evolution. 36 (8): 1746–1763. doi: 10.1093/molbev/msz099 . ISSN   0737-4038. PMC   6657726 . PMID   31070747.