Cancer is now the leading cause of disease-related death in dogs. Genetic and environmental factors have an important effect on the occurrence of cancer as well as prevention, diagnosis and treatment. Dogs and people are susceptible to many of the same types of cancer. The shorter life span of dogs and the availability of extended pedigrees with detailed family histories, provide a unique opportunity to study the causes and treatments of cancer that may benefit both dogs and people.

Ten years ago if a veterinarian was asked the breed with the highest incidence of cancer the answer would have been, unquestionably, the Boxer. Since that time several other breeds have been recognized as having a predisposition to certain cancers among them the Golden Retriever, Rottweiler, and Bernese Mountain Dog. Other breeds with a relatively low incidence of cancer include the Beagle, Poodle, Collie and Dachshund. Why do some breeds have a high rate of cancer while some others are rarely affected by it? The answer will come through the study of molecular biology and genetics.

The term cancer refers to a large number of diseases whose common feature is uncontrolled multiplication of cells. This loss of control over cell growth results from mutations or errors in the DNA code. During normal cell division in mammals there is an error rate varying from about one in one million to one in ten million in each base during each round of replication. Each daughter cell is likely to carry at least a few mutations in its DNA. Most of these mutations do not cause any problem to the cell's ability to function. However, others can disable tumor suppressor genes or activate genes that inhibit or promote cell division and survival.

Mutations that contribute to cancer risk can be inherited. An inherited mutation in a single gene that is important in cell growth control will increase the risk of developing cancer. In dogs there appears to be a predisposition among certain breeds to develop certain types of cancer suggesting that an hereditary component may be important in the development or progression of the disease.

When the cells composing a tumor, which inhabits an organ of the body, closely resemble the normal cells of that organ, they are said to be well-differentiated and may even function as the normal cells. Such tumor cells usually remain localized to the site from which they originated and have a very good long-term prognosis. That is, they are considered benign tumors (they produce no harm to the dog). In contrast, some tumors are composed of cells that have lost their resemblance to the original cell type. Such cells are said to be undifferentiated and have a greater likelihood of spreading to other parts of the body, a process known as metastasis. These latter tumors are considered malignant tumors and are responsible for various forms of cancer.

The tendency of some cancers to spread to distant sites in the body from the site of the original tumor presents the greatest challenge to successful treatment of cancer in the dog. Treatment failure is most often associated with metastasis, and in many cases, death is usually a result of organ failure due to spread of the cancer rather than from complications caused by the primary tumor. Growth of a tumor is dependent on penetration of blood vessels into the mass; therefore, malignant tumors usually secrete chemicals that induce new blood vessel formation. As tumor cells continue to divide, some will penetrate the walls of adjacent blood vessels or may invade the nearby lymphatic vessels and will be carried with the flow of blood or lymphatic drainage to distant sites within the body. Many of these circulating tumor cells will be destroyed in the blood stream or will die once they become deposited at a new organ site because they are not self-sufficient enough to colonize the new location. In contrast, a small percentage of these cells will have become independent. These autonomous cells are the seeds from which new tumors begin.

Many times when surgery was performed to remove a primary cancer the patient would die within a short interval following the procedure due to widespread invasion of cancer. It was believed that exposure of the cancer to air during the surgical procedure had caused the disease to spread rapidly. Recent findings, however, indicate that this phenomenon of rapid spread is associated with metastatic growth. It has been found that the primary tumor secretes factors into the bloodstream that actually inhibit the growth of new tumors. When the primary tumor is removed, cell division and tumor growth at these distant sites increase in the absence of these inhibitory factors. As a result, cancer may appear to spread quickly throughout the body, when in actuality, it had been present all along but at levels previously undetectable.

There is no single element or condition that causes cancer. Rather, cancer usually occurs as a result of a number of factors over an extended period of time. That cancer occurs with a higher frequency in older patients shows that the passage of time allows for the series of events required for a normal cell to transform into a cancer cell. Factors leading to increased risk compose two groups, those occurring in the environment (the carcinogens) and internal genetic factors (genetic defects).

Carcinogens: viruses, chemicals, physical carcinogens

Genetic defects: inherited gene defects and acquired chromosomal abnormalities

Some DNA and RNA viruses have the distinction of being called tumor viruses because they have been found to cause cancer in cells that they infect. These viruses accomplish this by integrating their own genetic material into the DNA of the infected cells. This integration of foreign DNA may alter the DNA message gene. When this event occurs, the gene is also changed structurally and functionally, This begins a chain of events which may lead to transformation of the normal cell into a cancerous cell. In some instances the virus will change into a cancer-causing agent that may be transmitted to other cells or animals. In other instances the infected cell's genetic material will only be passed on to daughter cells produced when the infected cell divides.

As opposed to viral infections that have been linked to only a fraction of cancers, chemical carcinogens are more likely to have a role in development of many more forms of cancer. Many toxic substances to which the body is exposed on a daily basis are insoluble, therefore, it the function of the liver, the primary organ responsible for filtration of the blood, through enzymatic reactions, to change insoluble compounds into soluble compounds so that they may be excreted from the body. Some toxic substances, however, require a longer reaction time to convert them to soluble products. If these compounds are highly reactive molecules, they may bind to and lead to alterations in the cellular DNA before they can be excreted from the body. Interestingly, in many cases the agent itself does not cause the alterations directly to the DNA. Instead, DNA damage occurs when normal mechanisms in the cell attempt to repair the DNA and in doing so, alter the correct sequence of DNA at the site of the bound agent. When this event causes permanent damage it is termed a mutation because the damage it produces may be passed on to other cells.

Physical Carcinogens (ionizing radiation, ultraviolet radiation, fiber and foreign-body related, and hyperthermia)

Living things are constantly bombarded by different forms of radiation: atomic particle radiation is given off by many minerals in the environment, and the sun is the source of both x-rays and ultraviolet radiation (UV). Both ionizing radiation and UV radiation change DNA by interfering with its cellular replication.. Specifically, ionizing radiation (atomic particle and x-rays) causes strand breaks in DNA chains while UV radiation creates chemical changes within the molecules called amino acids that compose the DNA. When much of a cell's DNA is damaged, the cell is often incapable of repairing this damage efficiently or quickly enough because its repair systems are over-extended.

In addition to the above mentioned environmental carcinogens, certain fibers have also been linked to induction of cancer. The most well-known of these is asbestos. However, glass and some plastics have also been implicated in having a role in the development of certain cancers. These fibers become foreign-bodies when they embed themselves into areas of the body (i.e. in the lungs through inhalation, in the digestive tract through digestion, or in the skin through contact). The cells surrounding the fibers will take-in the longer fibers that have a tendency to accumulate in the nuclei of the cells (the compartment of the cell where the DNA resides). Though the exact mechanism of how these fibers interact with the DNA to bring about cancer is not fully understood, it has been observed that chromosomes of cells harboring these fibers have large areas of missing DNA.

The role of hereditary defects in the development of cancer is very difficult to confirm. However, indications suggestive of a hereditary predisposition may include a family history of cancer and early age of onset.

While cancers attributed to carcinogens usually increase in occurrence in an age-dependent manner, cancers attributed to inherited genetic defects usually occur in young individuals. Since cancer occurs as a result of more than one genetic event, the time it takes for cancer to form may take many years. However, an inherited gene abnormality simply reduces the waiting period because the afflicted individual already has an internal predisposition to cancer. Inherited genetic defects usually occur when a mutation in a gene controlling tumor suppression is inactivated. Most of these mutations are autosomal dominant traits, so that even though the gene received from one of the parents is normal, all the cells of the offspring's body (the somatic cells) will carry a copy of the defective gene. When the somatic cells receive a second "hit" from an environmental carcinogen, there is an increase in the likelihood that cancer will develop.

Besides mutations affecting tumor suppressor genes, mutations in genes encoding protein for DNA repair mechanisms have been linked to certain hereditary conditions that are associated with increased cancer risk. Inability to repair even mild damage to the DNA increases the likelihood of a mutation in a tumor suppressor gene even in the absence of carcinogen exposure. These conditions are usually rare and are most often inherited as recessive defects. Also, mutations in genes that are responsible for metabolizing and eliminating carcinogens from the body may make an individual more susceptible to carcinogens in the environment and increase one's risk to certain cancers.

With a few exceptions, defects in the chromosomes are not inherited from the parental cells (egg and sperm), but occur during development and growth of the fertilized egg into a new individual by the process of mitosis (when cells duplicate their chromosomes in order to pass copies of the genetic information to each new daughter cell). Therefore, cancers associated with somatic mutations are not considered hereditary but, are attributed to acquired chromosomal defects. Implications for acquired chromosomal defects as a predisposing factor for cancer may include early onset of cancer in the absence of family history.

In addition to protecting the body from infectious micro-organisms, it is believed that the immune system also plays a role in identifying and eliminating cells that have transformed from normal cells to cancerous cells. Defects in the immune system play a role in the development of cancer. For example, very young and very old animals often have decreased immune-response and members of these age groups also demonstrate an increased susceptibility to effects of carcinogens. Animals that are purposefully immunosuppressed have demonstrated a greater likelihood of developing cancer when exposed to carcinogens while animals exposed to carcinogens but receiving immunostimulants often do not develop cancer. Furthermore, animals administered cancer causing viruses or chemical carcinogens often become immunosuppressed immediately following administration of these agents indicating that they stimulate an immune response.

Though it has been observed that congenital immunodeficiency diseases and acquired immunodeficiency syndromes (associated with immunosuppressive drugs and autoimmune diseases) are associated with increased risk for leukemias, lymphomas, and some sarcomas, these disorders do not increase risk for developing other tumor types. In light of this, it is believed that stimulation of the damaged lymphoid system by carcinogens is responsible for malignant transformation of lymphatic cells that give rise to these tumor types.

Evidence suggests that hormones are another internal factor that play a major role in the development of some cancers, particularly mammary, prostate, ovarian, thyroid, bone and testicular cancers. In the young, hormones provide the means by which the cells are signalled to divide so that growth and development of the organs and the individual can take place. In adults, hormones control cell growth in relation to various aspects of the reproductive cycle in both men and women. It is believed that excessive stimulation of certain organs of the body by hormones increases the likelihood of cancer.

The top five types of cancer seen in Boxers are Mast cell cancer (25%) Lymphoma (17%) and Lymphosarcoma (10%) meningioma (7%) hemangiosarcoma (5%). They are followed by lesser percentages of Oligdendroglioma, adenosquamous carcinoma, thyroid carcinoma, spindle cell sarcoma and others.

Weight loss, Vomiting and diarrhea, Trouble urinating, Poor appetite, Lethargy, Listlessness, Difficulty breathing, Difficulty swallowing, Discharge and/or blood from any body opening, Swellings or abnormal lumps, especially around the breast area in females or testicles in males, Seizures, Recurring infection, Depression, Lameness, Skin lesions, Localized pain, Enlarged lymph nodes

Mast cells are specialized cells that are naturally found in the body. They help an animal respond to inflammation and allergies. Mast cells release chemicals when stimulated, among them histamine, heparin, seratonin, and prostaglandins. These chemicals are vital to bodily function but can be damaging when released in chronic excess. Boxers along with Boston Terriers, bulldogs and beagles appear to be genetically predisposed to Mast cell tumors.

The most obvious sign of Mast cell cancer is a tumor. These tumors can appear anywhere on the body. There may be several together or just one. One characteristic of MCT is the tendency to change in size, even on a daily basis. For the most part, it is impossible to determine if a tumor is benign or malignant by its outward appearance. Therefore, when a tumor is discovered, the usual plan of action is to obtain a sample for examination under a microscope. This procedure is referred to as a biopsy.

Mast cell tumors are graded on a scale of 1 to 3. Grade 1 tumor cells are well-differentiated and appear to have good prognosis with no treatment beyond surgical removal. Grade 2 tumors are moderately differentiated and prognosis and treatment are difficult to predict. Grade 3 tumors are poorly differentiated and are considered very aggressive. They have a poor prognosis.

Systemic symptoms, depending on the location and the degree of spread, may include:

Loss of appetite, vomiting, bloody vomit, diarrhea, abdominal pain, dark or black feces, itchiness, lethargy, anorexia, irregular heart rhythm and blood pressure, coughing, labored breathing, various bleeding disorders, delayed wound healing, enlarged lymph nodes.

Dogs who have had mast cell tumors are more likely to develop more mast cell tumors. 50% of surgically removed mast cell tumors will re-grow in the same area.

Lymphoma accounts for approximately 20% of all canine tumors. Most of the time lymphoma appears as swollen glands (lymph nodes) that can be seen or felt under the neck, in front of the shoulders or behind the knee. If left untreated, dogs with lymphoma will generally live only 3 to 4 weeks.

Lumps appear under chin, tops of shoulders, on back of legs. Bumps appear suddenly, swollen glands in neck, female boxers- lumps in mammary glands, dramatic increase in thirst, metallic smell, may be restless.

Lumps have appeared on throat and/or shoulder areas (lumps have even been known to appear on eyelid), trouble breathing, trouble swallowing, dramatic increase of water consumption, badly swollen, and very hard glands just under jaw, possible mild seizure.

Sleeping for long periods of time, slow getting up, dazed at times, as if wondering where they are. Weight loss, loss of appetite, less playful. May become nervous and/or agitated because of pain. (Ex. Pacing floor, scratching walls, knocking things over)

Treatment for Mast cell tumors almost always starts with surgically removing the entire tumor. It is important to remove a wide margin around the edges of the tumor (2-3 cm) to insure that the area is clean. In some areas it is impossible to remove such a wide margin and area of cancerous cells may remain. Further surgery or radiation may be needed to treat any remaining cancer cells.

High-grade tumors may be treated systemically with prednisone and/or chemotherapy.

Chemotherapy is a second choice for treatment of cancer. As you can see from the information presented above, cancer is simply a normal process that is out of control. Cancer cells are identical to normal cells in every way except the control of cell division (cancer cells have lost the control of cell division). Chemotherapeutic agents are toxic chemicals that are used to kill the cancer cells. However, since all cells in the body are undergoing the exact same living processes, all chemotherapeutic agents kill normal cells as well as cancer cells. This is the reason why some dogs (and some people) get very sick during the chemotherapy. The drugs and the dose of those drugs that are used for chemotherapy are a delicate balance between killing the cancer cells and killing the normal cells of the body.

Radiation is the third mode of cancer therapy. Radiation has the potential to kill any cell in the body. Again, the idea of radiation therapy for cancer is to localize the destructive beam to the cancer, sparing the normal cells. This can be very successful when the cancer is a solitary nodule and the radiation beam can be focused on the cancer. However, when cancer is widespread (metastatic cancer) it is usually not possible to kill only the cancer cells and radiation is rarely a treatment under such circumstances.

Mammary Tumors (exception: inflammatory mammary cancer), Prostate Tumors, Oropharyngeal Tumor, Skin Cancers, Gastrointestinal Tumors, Lung Tumor, Bone Tumors

Risks associated with surgery increase with the age of the dog and are often associated with the overall health of the dog. Deaths resulting from surgery are most often associated with pulmonary blood clots (embolism), pneumonia, cardiovascular collapse, and primary disease. Cancer often causes a state of malnutrition in the dog which may further compromise the ability of the dog to recover from the trauma of surgery.

Other complications associated with surgery include abscess, wound infection, blood loss, and incomplete wound healing.

The principles of radiation therapy are the same as surgery: to cure the dog of cancer or to relieve the bulk of cancer in dogs with advanced disease while sparing normal tissues. Radiation produces its biologic effects when it comes in contact with the atoms of the dog's tissues. When radiation travels through these tissues, it causes excitation of these charged atoms that ultimately leads to biologic damage particularly in the form of DNA double-stranded breaks.

In some situations radiation therapy may provide advantages over surgery, particularly when tumor invasion is widespread or if the dog's general health places him at high risk for surgical complications.

Because of the clinical evidence of the effectiveness of radiation treatment of dogs with particular tumors an increased amount of veterinarians are beginning to offer this form of treatment for cancer and some benign tumors.

The higher the dose of radiation that a tumor is exposed to, the greater the chance for destroying all of the tumor cells. Unfortunately, however, high dose radiation also compromises the normal tissue that surrounds the tumor. A way to administer a high, total dose of radiation is to divide it up and administer it in small, equal amounts over a period of time; a procedure termed "fractionation," which reduces excessive complications in normal tissues.

Administration of treatment may be based on schedules of daily (Monday through Friday), alternate days (Monday, Wednesday, Friday), or twice-weekly treatments (Monday, Friday). During treatments, the dog is usually sedated or anesthetized to reduce movement and assure correct positioning.

Some tumors are sensitive to the effects of radiation and therefore, radiation therapy may be used as the only course of therapy with the intent to cure. Such malignancies include tumors of the brain that are often inoperable. Brain tumors respond well to radiation with either complete cures (as in the case of small pituitary tumors), or longer survival times (intracranial tumors and spinal lymphomas). Tumors of the nasal cavity can be difficult to control in terms of growth and invasion by surgical intervention. Additionally, surgical excision of these tumors often produces disfigurement and debilitation. Since these tumors are sensitive to radiation, there is an advantage for utilizing radiation treatment over surgery.

Limitations to the efficiency of radiation do exist, however. In larger tumors, there is an increased risk for the survival of cancer cells at the center of the mass: a condition that is often the reason the disease reappears at a later time. Therefore, veterinary oncologists often use radiation in combination with surgery and/or chemotherapeutic drugs to target residual disease that may escape radiation treatment alone.

Immediate side effects of radiation treatment result from old cells being replaced by new cells. The tissues which are at higher risk for damage by radiation exposure include the skin and the tissues lining the oral cavity, small intestine, rectum, and bladder. Tissue death (necrosis), non-healing ulcerations, organ dysfunction, and blindness are some of the common complications that may arise during radiation therapy.

Combining radiation and surgery for the treatment of cancer has the advantage of reducing the need for radical surgery, which often results in debilitating functional and cosmetic side effects. In veterinary oncology, radiation is most often used following surgery to destroy remaining cancer cells that may have been left behind. However, for the combination of radiation and surgery to provide additive efficacy over surgery or radiation treatment alone, only microscopic evidence of cancer can be left behind following surgery. If too much tumor remains, then advantages of using the combination are significantly reduced.

There are some drawbacks to administering radiation therapy following surgery. The first is that radiation therapy must be postponed until the surgical incision is completely healed. This unfortunately allows time for the regrowth of residual tumor cells which then increases the chance for failure to control the cancer. Secondly, cancer cells in the area of scar tissue are often more resistant to destruction by radiation. As an alternative, radiation therapy may be administered prior to surgery. Exposure to radiation prior to surgery has the advantage of often causing tumor masses to shrink and therefore lessens the extent of surgical invasiveness required to manage the disease. Radiation prior to surgery may reduce the risk for the spread of tumor cells during surgical excision of the tumor. This schedule also has its disadvantages. Radiation therapy prior to surgery may increase the risk for complications during and following surgery. Therefore, the veterinary oncologist must take into consideration what schedule of administration will provide the best outcome with the fewest complications based on each individual patient's disease.

In widespread cancers, which would require whole body irradiation to control the disease, is often not an option since an effective dose would exceed the limits of toxicity to the bone marrow. However, pre-clinical research exploring the use of bone marrow transplantation with whole-body irradiation in dogs with "multicentric lymphoma" suggests that this regimen may hold some therapeutic advantage for treating these patients.

Hyperthermia is not fully understood. It involves damage to cells through elevation of temperature. Heat exposure does cause conformational changes to proteins within the cells thereby altering the ability of cells to function. Therefore, it is believed that cell killing induced by hyperthermia may be a result of thermal effects on proteins.

The observation that high fevers in some human patients with cancer was associated with subsequent disease remission in these patients led to the idea that elevation of body temperature, a condition called hyperthermia, might provide a new treatment approach to this disease. Research into the use of hyperthermia for the clinical treatment of cancer has indicated that it is lethal to cells, causes tumor regression, increases the effectiveness of radiation therapy and enhances the action of many anticancer drugs.

Local heating of tumors is typically accomplished by microwave radiation, infrared radiation, radiofrequency or ultrasound. Hyperthermia is not a widespread practice in veterinary medicine at this time because it requires the use of specialized equipment.

Though cancer cells are destroyed by hyperthermia treatment alone, many factors including the nature and size of the tumor will influence the success of hyperthermia to eradicate the entire disease. Populations of cancer cells that may escape the lethal effects of hyperthermia are often resistant to subsequent heat exposure. Therefore, as with other methods of treatment, hyperthermia is often used in combination with radiation or chemotherapy to increase the chances of success. In canine cancer, treatment with hyperthermia is more commonly administered in combination with radiation.

Hyperthermia damages both cancer cells and normal cells. Toxicity may be significant when using this method of treating cancer.

Factors that make some cancer cells resistant to treatment with radiation (example: decreased blood flow) make these same cells particularly sensitive to hyperthermia. In dogs, combining hyperthermia with radiation against most types of tumors has improved the rate of success in eradicating the primary tumor which results in prolonged survival time. Unfortunately, however, many of these dogs later succumb to metastatic disease indicating the need to further combine this regimen with chemotherapy in an effort to control secondary disease due to metastases.

The principle of photodynamic therapy is based on the concept that when certain light-sensitive compounds (photosensitizers) are taken up by cells and then exposed to light, the compounds generate active molecules that are toxic to and kill the cells.

There are 2 steps to using PDT treatment. First the dog is administered a photosensitizer drug. In many cases, the photosensitizer is retained by the cancer cells but excreted from the normal cells of the body. After a period of time, the localized tumor is then exposed to light of a certain wavelength that will activate the photosensitizer. In veterinary oncology, PDT has been used limitedly and usually in dogs with localized, superficial, and minimally invasive tumors.

A previous limitation to widespread use of PDT was absence of data pertaining to the safe use of photosensitizers in dogs. In the clinical studies that have been conducted, however, there appears to be clear advantages to the use of PDT over radiation therapy in regard to the number of treatment sessions required to achieve therapeutic effectiveness.

A disadvantage of using PDT as a cancer treatment is the inability of light to penetrate deeply into tumor tissue. Therefore, treatment with PDT has been primarily aimed at superficial mucosal cancers, or those effecting the skin, lining of the bladder, and the lining of the oral cavity. Research to develop new classes of photosensitizers that are activated by longer wavelengths of light to allow deeper penetration into tumors is currently underway.

One of the major complications to the most common photosensitizer drug is the length of time the drug is retained within the body's tissues. After administration of this photosensitizer, the dog must remain in subdued light for 4-6 weeks to prevent damage to the skin.

The principle of chemotherapy is the treatment of metastasis. Localized treatment of tumors by surgery, radiation, etc. often fails because cancer cells from the tumor have already spread to other parts of the body. These metastatic cells eventually form new tumors even when the primary tumor has been eradicated.

Chemotherapeutic drugs have not been approved for use in veterinary medicine. This is mainly because of the high costs associated with drug licensing. Many studies indicating the effectiveness of chemotherapy to control and sometimes cure cancer in dogs has led many veterinary oncologists to include chemotherapy, either as the primary treatment or in combination with other forms of therapy, to treat cancer in the dog.

Many clinical studies have been conducted in dogs and extensive data has been collected to provide:

Information on which drugs provide the best control against specific tumor-types

Guidelines for treatment dosage

Information on what toxicities are expected.

Major disadvantages to chemotherapy are the toxicities associated with the action many of these drugs have against normal cells- particularly cells of the bone marrow, gastrointestinal lining, and hair follicles.

Common side effects resulting from toxicities include immunosuppression, anemia, nausea and vomiting, delayed wound healing, reproductive failure and hair loss. Some individual drugs may target specific organs including the heart, kidneys and central nervous system resulting in symptoms specific to these organ functions.

The use of a single chemotherapeutic agent is rarely successful in eradicating or curing the cancer. As with other types of therapy, not all tumor cells will be killed by a single agent. Veterinary oncologists tend to combat this by combining drugs having different mechanisms of action and non-overlapping toxicities with the goal to target a broader range of cancer cells while preventing the development of new resistant generations of cells.

In veterinary medicine, lymphoma has been the most extensively studied form of cancer in regard to combination drug treatment.

Certain drugs act as radiosensitizers, thereby increasing the success of radiation treatment. In veterinary medicine, the chemotherapeutic drugs "Cisplatin" and "Carboplatin" have been studied extensively for their radiosensitizing effects. These drugs are given simultaneously with radiation treatment and often have direct toxic effects on cells in addition to increasing cellular sensitivity to radiation.

Combinations of "Cisplatin" and radiation followed by surgery have been successfully used in dogs with Osteosarcoma and resulted in a one year rate of remission in 92% of treated dogs. Even in dogs not considered candidates for surgery, the combination of "Cisplatin" and radiation was successful for providing soothing treatment of osteosarcoma without increasing complications associated with radiation. This combination is also effective in the treatment of advanced carcinomas of the head, neck and urinary bladder and sarcomas.

Some drugs work more efficiently when above normal body temperature. Therefore, these drugs when combined with hyperthermia treatment are expected to increase the effectiveness of certain drugs to kill tumor cells.

The theory behind gene therapy is to introduce foreign DNA into a cancer cell which when incorporated into that cancer cell, will usually begin that cells destruction. There are primarily four approaches to gene therapy:

Suicide gene therapy where the protein product of that gene changes an inactive drug into a toxic drug only in the cancer cell carrying the foreign gene

Genetic immunotherapy where the foreign gene causes the cancer cells to express certain molecules on their surfaces that will attract components of the immune system to attack and destroy the cancer cells

Tumor suppressor gene therapy where the foreign gene replaces a mutated gene that has caused unregulated cell growth in the cancer cells

Drug resistance gene therapy where a foreign gene which makes cells resistant to chemotherapy drugs is introduced into a patient's normal cells so that the patient may be administered higher doses of chemotherapy with reduced chances of toxic side-effects.

Gene therapies utilize a number of methods, including viral and non-viral vectors to deliver genetic material into cells. As such, each of these delivery systems has advantages and disadvantages, and to date is still undergoing clinical evaluation for effectiveness and safety issues.

Genetic immunotherapy has been the most explored form of gene therapy for the treatment of dogs with cancer.

In one study dogs with malignant melanoma, a very aggressive form of cancer, who were previously treated with surgery and radiation treatment were treated with green-monkey kidney cells expressing interleukin-2 (IL-2) DNA. Twelve months after treatment, dogs treated with the genetic immunotherapy had a 37% survival rate compared to a survival rate of only 6% in dogs that did not receive the genetic immunotherapy.

It is believed that the IL-2 expressing cells caused an inflammatory response at the site of the cancer and brought about an immune response that caused an anti-tumor effect.

In another study, when IL-2 gene therapy was combined with a bacterial gene to enhance the immune effect in dogs with advanced metastatic melanoma (lymph node metastasis), 45% of the dogs showed either complete or partial remissions of tumors with significantly longer survival times compared to untreated dogs. Additionally, no adverse side-effects were observed in any of the dogs treated!

For cancer cells to divide and become solid tumors they are dependent upon the formation of blood vessels, a process known as angiogenesis, that will provide blood flow with oxygen and nutrients to the developing tumor. Many cancer cells excrete molecules into the surrounding tissues that fuel the formation of new blood vessels. Based on these observations, the idea of preventing tumor growth by cutting off blood supply to the tumor was developed. Natural and synthetic inhibitors of vascular formation, known as anti-angiogenic drugs, have been purified, formulated and assessed for their abilities as anti-tumor agents. Such drugs include angiostatin, thrombospondin, and endostatin. In preclinical animal studies, anti-angiogenic drugs have been found to significantly inhibit tumor growth and in some instances produce tumor regression.

Many of these anti-angiogenic drugs are in the early stages of clinical development for treatment of human cancers. Although there are several ongoing canine studies using these drugs as well, there currently is no clinical information available on treatment effectiveness.

This summary is going to be heavily focused on the treatment protocol developed for Ruby a four year old white boxer.

Ruby was diagnosed with lymphosarcoma in mid June 2002. The vets advised chemotherapy as the only treatment available to extend Ruby's life.

Ruby's owner Darlene consulted with a holistic vet. Upon the recommendation of the holistic vet Ruby was switched over to a mostly raw diet, which included some grains such as brown rice and oatmeal1.

The supplements Ruby was put on were all designed to stimulate her immune system. The supplements include the following:

Vit C-1000 mg/day
Vit E- 400 UI - 2/day
Flaxseed Oil - 1tsp-1TBS/Day
Garlic - 1 clove/day
Canine Plus (copper, zinc, selenium, Amino Acids: Arginine,Glutamine,methionine,bromcystine, L-aspergine)
Coenzyme Q102
Shark Cartilage3
Essiac tea4
Hoxey Formula POWER mushrooms (Shitake & Ganoderma Mushrooms) for 3 months
Chih-ko &Curcumen for 1 month
Galium-Heel for 2 weeks
Scrophularia for 30 days
Lymphomyosot for 3 weeks
Modu-Care
Oncolyn

The only conventional treatment prescribed for Ruby was prednisone to help decrease the size of the lymph nodes.

Ruby has gone in for monthly blood tests. In August Ruby's blood work showed no circulating lymphocytes and x-rays taken showed no sign of cancer in any of her organs.

At the end of September Ruby's prednisone dosage was reduced substantially from the original dosage. After a course of Clavamox5, Ruby became ill (nausea, vomiting and diarrhea). After 4 days Ruby visited the vet who indicated the lymph glands in her digestive tract were most likely inflamed and causing a blockage. His prognosis was grim.

Ruby's owner took it upon herself to increase the prednisone dosage to the original amount prescribed. With 12 hours Ruby was greatly improved.
The diet aspect of the treatment protocol is crucial. Cancer cells feed on sugar, carbohydrates convert to sugar. From what I've read I don't think the difference between simple and complex carbohydrates is relevant in this case. In "Complementary and Alternative Veterinary Medicine", Dr Gregory K. Ogilvie indicates that the ability to metabolize carbohydrates is altered dogs with cancer. He further goes on to state "that dogs with cancer have a reduced amount of carbohydrates in their diet".

After returning from a conference this past week (Sept 30, 2002), Ruby's holistic veterinarian has recommend the discontinuation of all grain in Ruby's diet.

Since this recommendation, Ruby's protocol is now consistent with what I have found during my research.

One of the biggest problems dogs with cancer face is cachexia, or progressive involuntary weight loss. Dr Ogilvie recommends adding much more fat to the diet in the form of omega fatty 3 acids. The omega fatty 3 acids will help with energy and have shown they can help stop tumour growth.

The diet for a cancer stricken dog should include raw chicken, eggs, beef, fish and organ meat.

Vegetables can include broccoli, celery, cabbage (red and green) bok choy, collards, turnip greens, spinach, summer squash (zucchini and crook neck) and chinese cabbage. No sweet vegetable should be give (ie: carrots, peas, corn, pumpkin, potatoes). Fruit should be generally avoided.

It would also behove us to keep in mind the possible role over vaccination plays in the development of cancer. Catherine O'Driscoll writes, "Vaccine components have been found at the cancer sites of victims. Worse, they have been found at the cancer sites of the CHILDREN of the people who received the guilty vaccine. In other words, vaccines can cause inheritable cancer".

Dr. Don Hamilton, DVM writes, "Vaccination is not as widely and unquestionably accepted today as it was in the past. Many pet guardians and veterinarians believe we have taken the concept much farther than its usefulness warrants. In twenty years of veterinary practice, I have made the transition from believing strongly in the protective power of vaccines to becoming continually more certain that they create at least as much illness as they have ever prevented. In truth, I now consider vaccination to be tantamount to animal abuse in most cases".

Ruby's visit with the holistic vet on Oct 14 was not a happy event. Her blood work showed extensive lymphocyte activity and many of her internal organs are enlarged. The vet doesn't believe much more can be done for Ruby except to make her comfortable.

I am sad to report Ruby lost the battle with her lymphosarcoma on November 8, 2002....Ruby was a fighter to the end, it was only in the last couple of days she showed any signs of illness.

If there is any good that came out of Ruby's battle it is the knowledge we gained about her treatments and diet, and that she survived as long as she did with only holistic treatment. Using hindsight, I think if she had some chemo along with the holistic treatment, she would have had more time.

References:

http://www.altvetmed.com/Cancer.html
http://www.cfnaonline.com/caninetimes/resource-center/cancer/cancer.shtml
http://www.doglogic.com/healthlinks2.htm
http://www.everglo-naturalvet.com/pdf/Cancer_Autoimmune.pdf
http://www.b-naturals.com/sum98.htm
http://www.csucancercure.com/wbswebpage.cfm?pagetextid=CAVM
http://www.adoredbeast.com/vaccines.shtml

The Nature of Animal Healing, Dr. Martin Goldstein (Knopf; ASIN: 0679455000; April 1999)

Protein-calorie malnutrition, a condition known as "cancer cachexia", is often a debilitating side-effect of cancer in both humans and dogs.

Symptoms of cancer cachexia include:

Diminished appetite and food intake
Progressive weight-loss
Metabolic abnormalities.


Many patients will suffer from severe debilitation and eventual death, therefore attention must be given to ensuring that dogs afflicted with cancer receive palatable, highly digestible, and energy-dense diets that may enhance their overall quality of life, their life expectancy, and their ability to undergo aggressive therapy regimens for treatment of their disease.

Dietary recommendations for dogs with cancer include high-fat (greater than 40-50% of calories) diets that are low in carbohydrates. Premium dog foods offering special "performance" or "stress" formulas are considered appropriate for the critically ill cancer patient. Unfortunately, however, many of these dogs are unwilling or unable to eat for themselves. Therefore, handfeeding and in many cases, feeding tubes or catheters should be used to ensure adequate nutrition. Use of appetite stimulants are sometimes used but may only produce immediate results regarding food intake and does not increase food intake over time. Because of this, some veterinarian oncologists prefer to use feeding tubes or catheters that assure increased food intake instead of appetite stimulants.

Certain conditions and factors have been found to increase risk of cancer in dogs. This includes unilateral or bilateral "cryptorchidism" (retention of one or both testicles in the abdominal cavity) which increases risk of testicular cancer in male dogs and benign mammary tumors which increase risk for mammary cancer in female dogs.

As such, cancer prevention in the form of castration (neutering) and ovariohysterectomy (spaying). Removing these non-vital organs associated with these forms of cancer by either spaying or neutering your dog at an early age prevents this type of cancer in your dog.

Risks associated with surgery increase with the age of the dog and are often associated with the underlying health. Mortalities resulting from surgery are most often associated with pulmonary blood clots (embolism), pneumonia, cardiovascular collapse, and primary disease. Furthermore, in addition to its secondary effects on patient metabolism and immunity, cancer often causes a state of malnutrition in the dog which may further compromise the ability of the dog to recover from the trauma of surgery.

Other complications associated with surgery include abscess, wound infection, blood loss, and incomplete wound healing.