Cancer, or neoplasia, is the uncontrolled growth of cells due to damage to DNA (mutations).
The cause(s) of cancer are complex and often multi-factorial. A leading trigger is chronic inflammation, from UV light, environmental chemicals, etc., accounts for approximately 25% of cancer cases, and viruses, bacteria and parasites contribute to a further 17.8% of the global burden of human cancer. A significant proportion of the remainder is attributed to genetic predisposition. A similar scenario is seen with cats. At present, it is believed that cancer results from a subset of cancer stem cells that do not mature into terminally differentiated cells but instead continue to proliferate. Certain cancer cells can express the same surface markers as do stem cells, providing support for this theory.
Carcinogenic compounds result in chronic inflammatory conditions where reactive oxygen and nitrogen species are generated from inflammatory and epithelial cells, causing DNA damage that leads to neoplasia. Current models of cancer stemming from a single mutant cell leading to monoclonal proliferation is being challenged in light of mesothelioma in humans, where it has been found to arise from multicellular mutations (aneuploidy theory of cancer). This may become a more dominant paradigm in future research.
At the cellular level, neoplastic cells, generally speaking, have been shown to utilize more glucose than normal cells in vitro and in vivo. As a consequence, cholesterol accumulates in neoplastic sites as a result of increased rates of glucose uptake. This in turn increases signalling between cancer cells via stimulation of various growth factors, with consequential migration, invasion, and angiogenesis of cancer cells. Glucose uptake is mediated by a number of unique glucose transporter proteins. Maintenance of glucose transport appears to be an essential feature of the survival response of hemopoietic cells. Studies on human leukemia cells has demonstrated that small changes in cell surface cholesterol content results in drastic alterations in glucose transport regulation. Interference with glucose transport via cholesterol-ligating drug have been shown to interfere with metastatic cancer cell receptors.
From a clinical perspective, neoplastic diseases in cats must be distinguished from:
- autoimmune diseases such as pemphigus and Immune-mediated haemolytic anaemia, which arise from an overactive immune response of the body against substances and tissues normally present in the body.
- tissue associated with new growth (hyperplasia/fibroplasia - e.g. feline eosinophilic gastrointestinal fibroplasia), abnormal growth (dysplasia) and shrinkage (anaplasia).
- transplant rejection - immune attack of foreign tissues
|Adenocarcinoma (pulmonary)||a rare and usually fatal disease in cats|
|Basal cell tumour||a common cell tumour of the skin with variable malignancy|
|Biliary carcinoma||a rare cancer of the gall bladder of cats|
|Bladder (urinary) cancers||a rare form of cancer in cats|
|Brain tumours||a rare form of cancer in cats, usually untreatable|
|Carcinoma||list of common tumours of epithelial tissue|
|Chemodectoma||a rare tumour of the aortic body, common in cats living at high altitudes|
|Chondrosarcoma||a rare tumour of cartilage which affects the nasal cavities and surrounding sinuses|
|Digit (paw) tumours||rare tumours affecting the feet of cats, usually requiring surgical excision|
|Ear tumours||common, fast growing tumour of skin inside the ear canal. Surgical excision is preferred treatment|
|Epulides||a tumour of the oral gums, often malignant in cats|
|Fibrosarcoma||a rare skin cancer associated with reactions to feline vaccines containing adjuvants|
|Fibropapilloma (sarcoids)||a rare skin cancer often seen in farm cats|
|Giant cell tumours||a rare tumour of bone|
|Globus tumours||a rare tumour of blood vessels with high malignancy|
|Hamartoma||a rare vascular malformation/cancer in cats|
|Haemangioma||rare, benign vascular growths|
|Haemangiosarcoma||a rare and often fatal blood cell cancer|
|Hepatic tumours||rare tumours of the liver of cats|
|Histiocytic disease||a rare tumour of skin, showing as single or multiple nodules|
|Lipoma||a tumour composed entirely of fat cells. Rarely malignant. Surgical excision is preferred treatment|
|Leukaemia||a rare type of cancer, often associated with infection with FeLV virus|
|Liver tumours||infrequent cancers, often associated with lymphoma|
|Lymphangiosarcoma||a tumour of the lymph system, with high malignancy and morbidity|
|Lymphoreticular tumours||rare tumours of bone|
|Lymphoma||a cancer of lymph nodes, similar to Hodgkin's Disease in humans|
|Lymphosarcoma||one of the most common types of internal cancers in cats, usually in cats over 8 years of age|
|Mammary tumours||a common tumour in queens requiring mastectomy|
|Mast cell tumour||a common skin tumour which can metastases but usually has a good prognosis post-surgical excision|
|Melanoma||a rare skin cancer with high mortality rates|
|Multiple myeloma||a rare, fatal tumour of plasma cells in cats|
|Nerve sheath tumor||rare in cats, arise in cranial and peripheral nerve roots and nerves. Classifications as Schwannoma, neurofibromas or neurofibrosarcoma of little clinical significance|
|Oral neoplasia||rare, usually malignant forms of cancer|
|Osteochondromas||a rare bone cancer of cats|
|Osteosarcoma||a rare bone cancer affecting limbs of the cat, usually malignant|
|Pancreatic carcinoma||usually malignant, rapid onset and high mortality rates in older cats|
|Papilloma||usually benign tumours of mouth and feet|
|Paraneoplastic disorders||a neoplasia-associated alteration in bodily structure / function distant to the tumour|
|Parosteal osteosarcoma||second most common type of bone cancer in cats|
|Plasmacytoma||a rare skin cancer of cats|
|Round cell tumor||usually affects lymph nodes, includes various types such as mast cell tumors, histiocytomas, epithelial lymphomas|
|Sebaceous tumours||a common skin tumour of cats, usually non-malignant|
|Squamous cell carcinoma||the most common and treatable form of cancer in cats|
|Subungual carcinoma||tumour of toenail-bed in cats|
|Teratoma||a rare cancer formed from germ cells|
|Testicular cancer||primarily Sertoli cell cancers, usually malignant|
|Thymoma||a relatively benign tumour of the thymus causing general physical disease|
|Thyroid hyperplasia (Hyperthyroidism)||a benign thyroid tumour readily treated with medication and/or radiation therapy|
|Urinary cancers||a rare form of cancer in cats|
|Vaccine- and microchip-associated sarcomas||a cancer as a result of certain types of vaccines|
Chemotherapy in feline medicine follows in parallel with advances in human medical chemotherapy. One of the most common skin cancers in cats, squamous cell carcinoma, is rarely approached chemotherapeutically, but a common gastrointestinal cancer, mesenteric lymphosarcoma is relatively successful when treated with modern agents such as cyclophosphamide, chlorambucil and/or prednisolone.
Broadly, most chemotherapy drugs work by impairing mitosis (cell division), effectively targeting fast-dividing cells. As these drugs cause damage to cells they are termed cytotoxic. Some drugs cause cells to undergo apoptosis (so-called "cell suicide").
Unfortunately, scientists have yet to be able to locate specific features of malignant and immune cells that would make them uniquely targetable (barring some recent examples, such as the Philadelphia chromosome as targeted by imatinib). This means that other fast dividing cells such as those responsible for hair growth and for replacement of the intestinal epithelium (lining) are also affected. However, some drugs have a better side-effect profile than others, enabling doctors to adjust treatment regimens to the advantage of patients in certain situations.
As chemotherapy affects cell division, tumours with high growth fractions (such as acute myelogenous leukemia and the lymphomas, including Hodgkin's disease) are more sensitive to chemotherapy, as a larger proportion of the targeted cells are undergoing cell division at any time.
Chemotherapeutic drugs affect "younger" tumours (i.e. more differentiated) more effectively, because mechanisms regulating cell growth are usually still preserved. With succeeding generations of tumour cells, differentiation is typically lost, growth becomes less regulated, and tumours become less responsive to most chemotherapeutic agents. Near the centre of some solid tumours, cell division has effectively ceased, making them insensitive to chemotherapy. Another problem with solid tumours is the fact that the chemotherapeutic agent often does not reach the core of the tumour. Solutions to this problem include radiation therapy (both brachytherapy and teletherapy) and surgery. In the past two decades, numerous experimental, clinical, and epidemiologic studies have linked tumour development and progression with the presence of cyclo-oxygenase (COX) in tumour cells in humans. A similar relationship between inflammation and oncogenesis seems to occur in cats associated with sarcomas and vaccines/microchips. COX enzymes exist as two different isoforms and catalyse conversion of arachidonic acid to an array of prostaglandins. COX-1 is expressed constitutively in many cells and is involved in normal physiologic activities such as cytoprotection of the gastric mucosa, regulation of renal blood flow, and platelet aggregation. COX-2 is an inducible enzyme that is involved in the production of prostaglandins, which modulate pathologic events such as inflammation, wound healing, and neoplasia. A variety of agonists including cytokines, growth factors, and oncogenes can induce COX-2 expression. COX-2 immunoreactivity is found in a number of human tumours including colon, lung, breast, gastric, prostatic, head and neck, and bladder carcinomas. More recently, COX-2 has been demonstrated in canine squamous cell, renal cell, and transitional cell carcinomas, prostatic adenocarcinomas, and intestinal neoplasias.
Recent studies also demonstrate that non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit COX enzymes, can reduce the incidence of cancer in humans and experimental animal models and may be potential targets for therapeutic and preventive strategies. Importantly, the relative risk of developing epithelial cancer, including colonic carcinoma, is lower in persons receiving aspirin therapy. In veterinary medicine, dogs with transitional cell carcinoma of the urinary bladder may have complete or partial reductions in tumour size when treated with piroxicam, a potent NSAID. Recently, anti-tumour activity was reported in dogs with oral squamous cell carcinoma treated with piroxicam.
The use of traditional herbal medicine has also gained ground in recent years with the efficacy of drugs such as artemisinin and triptolide showing promise when used either alone or in combination with conventional chemotherapeutic agents.
Diagnosis of feline cancer
- ↑ Vennervald BJ, Polman K. (2009) Helminths and malignancy. Parasite Immunol 31(11):686-96
- ↑ Sell S & Leffert HL (2008) Liver cancer stem cells. J Clin Oncol 26:2800–2805
- ↑ Crowe DL et al (2004) Relationships between stem cells and cancer stem cells. Histol Histopathol 19:505–509
- ↑ Hiraku Y. (2009) Formation of 8-nitroguanine, a nitrative DNA lesion, in inflammation-related carcinogenesis and its significance. Environ Health Prev Med Nov 19
- ↑ Duesberg P et al (2000) Aneuploidy precedes and segregates with chemical carcinogenesis. Cancer Genet Cytogenet 119(2):83-93
- ↑ Comertpay, S et al (2014) Evaluation of clonal origin of malignant mesothelioma. Journal of Translational Medicine 12(1):301
- ↑ Casalou C et al (2011) Cholesterol regulates VEGFR-1 (FLT-1) expression and signaling in acute leukemia cells. Mol Cancer Res 9(2):215-224
- ↑ Raghu H et al (2010) Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells. BMC Cancer 10:647
- ↑ Caliceti C et al (2012) Effect of plasma membrane cholesterol depletion on glucose transport regulation in leukemia cells. PLoS One 7(7):e41246
- ↑ Popa I et al (2014) Expression and subcellular localization of RAGE in melanoma cells. Biochem Cell Biol 92(2):127-136
- ↑ Dernell WS et al (1998) Principles of treatment for soft tissue sarcoma. Clin Tech Small Anim Pract 13(1):59-64
- ↑ Beam, SL et al (2003) An Immunohistochemical Study of Cyclooxygenase-2 Expression in Various Feline Neoplasms Vet Pathol 40:496-500