BIOCHEMISTRY OF CANCER

BIOCHEMISTRY OF CANCER

INTRODUCTION

The revolutionary advances in cellular and molecular biochemistry in the last quarter century have provided an unprecedented opportunity for systematic approaches to understand the cancer process. With these new advances and the knowledge acquired as a direct result, an enormous impact has positively affected the clinical areas of cancer prevention, disease management, and treatment of malignancy. Despite these scientific achievements, we are still faced with the challenge of fully understanding the complex nature of cancer, including issues of disease recurrence and drug resistance (Wilbur, 2009).

Cancer is a set of diseases in which cells escape from the control mechanisms normally limiting their growth. Cancer cells ignore the normal signals that operate the cell cycle and affect the body by dividing uncontrollably and invading surrounding tissues. The gene regulation systems that go wrong during cancer turn out to be the very same systems that play important roles in embryonic development, the immune response, and many other biological processes.The genes that normally regulate cell growth and division during the cell cycle include genes for growth factors, their receptors, and the intracellular molecules of signaling pathways. mutations that alter any of these genes in somatic cells can lead to cancer.

Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth. The heritability of cancers is usually affected by complex interactions between carcinogens and the host’s genome. New aspects of the genetics of cancer pathogenesis, such as DNA methylation, and microRNAs are increasingly recognized as important (MacDiarmid, et al., 2020).

Cancer is simply the gain of oncogenes and the loss of tumor suppressor genes. Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting oncogenes are typically activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Activated oncogenes result form different types of mutations including point mutations, chromosomal translocations, promoter translocations, and amplifications. Point mutations increase proteins’ activity and prevent it from being turned off. Chromosomal translocations encode fusion proteins that are hyperactivated or inappropriately regulated or localized. Promoter translocations drive abnormally high levels of expression. Amplifications increase the copy number and expression of a gene. Tumor suppressor genes (TSG) are then inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system. Tumor suppressor genes can be inactivated by missense mutations that decrease the protein’s activity, deletions, frameshifts, and promoter methylation (MacDiarmid, et al., 2020)..

Diagnosis usually requires the histologic examination of a tissue biopsy specimen by a pathologist, although the initial indication of malignancy can be symptoms or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments (MacDiarmid, et al., 2020)..

History of Cancer

The word cancer comes from the Greek physician Hippocrates. He used the Greek words “carcinos” and “carcinoma”, meaning crab in Greek, to describe cancer because he believed that tumors resembled crabs. The two words were combined into one: “karkinos”.

The oldest record of cancer is from the Egyptians around 1500 B.C. The Edwin Smith Papyrus documents 8 cases of breast tumors treated with cauterization, a method of destroying tissue with a hot instrument called a “fire drill”. Records indicate that there were no treatments for the disease. In addition, archaeological finding has discovered mummies with fossilized bone tumors suggestive of bone cancer. Also in the Papyrus, it is suggested that Egyptian physicians could differentiate malignant tumors from benign tumors.

Later, the city of Constantinople became the Medical Center of the World. During this time period, the cause of cancer was attributed to an excess of black bile. This was based on Hippocrates’s idea that the human body was composed of four different types of bodily fluids: blood, phlegm, yellow bile and black bile. Any excess or deficiencies in either fluid would cause disease, and in this case, excess of black bile was believed to cause cancer. This was the knowledge for the next 1400 years, through the Middle Ages, and went unchallenged since religious superstition at the time prohibited doctors from performing autopsies (MacDiarmid, et al., 2020)..

In the 15th Century Renaissance, physicians began to acquire more knowledge on human physiology. Giovanni Morgangni, in the 16th century, began to do autopsies on the bodies of the deceased in order to discover a pathological relationship between disease and death. Also, during this time, a Scottish physician named John Hunter suggested that cancerous tumors may be removed by surgical means. In the 17th Century, the Black Bile theory was replaced with another theory called the Lymph theory. The idea was that cancer was caused by degenerating and fermating lymph.

In the 19th Century, Rudolf Virchow, who is considered the father of cellular pathology, linked the clinical course of illnesses with pathological findings. This discovery allowed physicians to not only assess the damage of a particular cancer on the body, but also laid the foundations of cancer surgery. Tissues removed from the infected area could rapidly and quickly assessed to determine the type of cancer and also to elucidate whether or not the tumor was completed excised.

The 20th Century saw a rise in cancer knowledge. Research on carcinogens, radiation therapy, and better means of identification were discovered. There was tremendous scientific improvement on the understanding of cell growth and division mechanisms.

ETIOLOGY OF CANCER

All cancers are multifactorial in origin. They include genetic, hormonal, metabolic, physical, chemical and environmental factors. Most human cancers are spontaneous. Biochemistry of Cancer Chapter 48 Chapter at a Glance The learner will be able to answer questions on the following topics: ¾ Mutagens and carcinogens ¾ Oncogenic viruses ¾ Oncogenes and oncosuppressor genes ¾ Oncofetal antigens ¾ Tumor markers ¾ Anticancer drugs ¾ Tumor immunology All cancers originate usually from one aberrant cell, which goes on to multiply and produce a tumor mass. One mutation occurs out of 106 cell divisions. By the time a person reaches adulthood, about 1026 cell divisions have occurred. Thanks to the surveillance by the immune system, these aberrant cells are usually destroyed. As age advances, the number of mutations accumulate, hence the statistical probability of the incidence of cancer is increased. No wonder, cancer is a disease of old age, especially after 60 years. Cancer is the second most common cause for death in developed countries, second only to cardiovascular diseases (Zuckerman et al., 2009).

Mutagens

 Any substance which increases the rate of mutation can also enhance the rate of incidence of cancer. Therefore, all carcinogens are mutagens. Examplesare X-rays, gamma-rays, ultraviolet rays. Some human cancers are caused by chemicals. These may be introduced into the body by means of

• Occupation (aniline, asbestos),
• Diet (aflatoxins) or
• Lifestyle (smoking).

Chemical carcinogensact cumulatively. Tobacco, food additives, coloringagents, and aflatoxins are common carcinogens inour environment.Thousands of chemicals are known mutagens and carcinogens.

Aflatoxins: They are a group of chemically related compoundssynthesized by the fungi, Aspergillusflavus. Themould grows on rice, wheat and groundnut, whenkept in damp conditions. The fungi may grow in cattlefodder, which may enter into human body throughthe cow’s milk. Aflatoxins are powerful carcinogens,which produce hepatomas.

Cigarette: Lung cancer is associated with the habit of cigarettesmoking. Cigarette contains many carcinogens, themost important group being benzo(a)pyrenes. Otherimportant deleterious substances in cigarette smokeare nicotine, carbon monoxide, nitrogen dioxide andcarbon soot. Statistically, it is estimated that onecigarette reduces 10 minutes from the lifespan of the individual. The incidence of lung cancer is increased to 15 times more in persons smoking 10 cigarettes perday and 40 times more when smoking 20 cigarettesper day. Thus, WHO suggested the slogan ‘Cigarettesmoke is injurious to health’. Moreover, non-smokingspouse of a heavy smoker will have 5 times moreprobability to get lung cancer than a non-smoker.

Progression: The biological history of a tumor shows progressionof malignancy. Cells with faster growth rate havea selection advantage. Thus, cells with increasedmalignant character are progressively selected.Familial adenomatous polyposis is a typicalexample for multistep progression. Mutations inthe APC gene are inherited from parents. By thetime the patient becomes adult, there will be differentdysplastic aberrant crypts in the large intestine. Someof the cells will get somatic mutations in the K-Rasgene; these will progress to form adenomas. Further mutation in TGF gene or p53 gene or Baxgene willgive the push for the development of malignancy.

ACTION OF CHEMICAL CARCINOGENS

Mechanisms of action of chemical carcinogensare:

• Carcinogens are generally electrophiles(molecules deficient in electrons); they readilyattack nucleophilic (electron rich) groups of DNA,
• Carcinogens may bind covalently to cellular DNA.N2, N3, and N7 atoms of guanine are highly prone toaddition of carcinogen groups, (c) These changes willlead to DNA alterations, in spite of DNA repair, withincreased probability of mutations.

Physical Carcinogens

X-ray, gamma-ray and UV-ray may cause:

• formation of pyrimidine dimers,
• Apurinicsites withconsequent break in DNA, and
• Formation of freeradicals and superoxides which cause DNA break,leading to somatic mutations.

Exposure of X-ray infetal life will increase the risk of leukemia in childhood.

ANTIMUTAGENS

1. These are substances which will interfere withtumor promotion. Vitamin A and carotenoids areshown to reverse precancerous conditions.
2. Vitamin E acts as an antioxidant, preventing thedamage made by free radicals and superoxides.
3. Vitamin C regularly given to persons workingwith aniline prevented the production of newcancer cases.
4. Tubers, beans and leafy vegetables are shownto interrupt tumor promotion.
5. Curcumin, the yellow substance in Turmeric isknown to prevent mutations.
6. The beneficial effect of the fiber content of thediet is described in Chapter 35. Low protein, lowfat, diet decreases the risk of cancer in animalstudies.
7. Flavinoids are phytochemicals that possessantimutagenic properties. Phenolic compoundsfound in fruits like grapes, strawberries, walnuts,etc. are found to be antimutagenic. Green teais shown to be effective against smoke inducedmutations.

ANTICANCER DRUGS

Surgery and radiotherapy are most effective to reducethe initial tumor load. These are the prime modalities oftreatment in solid tumors. Chemotherapy is the sheetanchor of therapy in leukemias, advanced lymphomas,choriocarcinoma and other widely disseminated malignancies.The effectiveness of cytotoxic drugs is directlyproportional to the doubling time of the tumors, and isinversely proportional to the number of cancer cells (Campbell et al., 2008).

Cytotoxic drugs affect all the cells which are in the dividing phase. Rapidly dividing normal cells (gastrointestinaltract, hematopoietic system, hair follicles, gonads) arealso affected by chemotherapeutic drugs, leading totoxicity. In fact, pharmacological dose and toxic doseusually overlap in the case of these drugs.

Methotrexate: It inhibits dihydrofolatereductase. Methotrexatehas structural similarity to folic acid, and hence willcompetitively inhibit folate reductase. So in presenceof methotrexate, tetrahydrofolic acid is not produced,which is necessary for incorporation of C2 and C8of purines and C5 methyl group in thymidine. Thus,there is inhibition of DNA synthesis and consequently of cell division. Methotrexate is commonly employedin the treatment of choriocarcinoma, which is acurable cancer. It is also useful in acute leukemia.

6-Mercaptopurine: It is a purine analogue which prevents amination ofIMP to AMP, so that the availability of AMP is reduced. This leads to inhibition of synthesisof DNA, and in turn cell division. It is commonlyemployed in treating acute lymphoblastic leukemia.

Monoclonal Antibody: These drugs are a relatively new innovation in cancer treatment. The mechanismof action of monoclonals against cancer may be:

1. The antibody marks the cancer cell and makes iteasier for the immune system to attack. The drugrituximab attaches to CD20 found only on Bcells; makes the cells more visible to the immunesystem, which can then attack.
2. Block growth factors. Certain cancer cells makeextra copies of the growth factor receptor. Thismakes them grow faster than the normal cells.Monoclonal antibodies can block these receptorsand prevent the growth signal. For example,Cetuximabattaches to epidermal growth factorreceptors (EGFR) on cancer cells. Blocking thissignal from reaching its target on the cancer cellsmay slow or stop the cancer from growing.
3. Stop new blood vessels from forming. Toattract blood vessels, cancer cells send outgrowth signals. Monoclonal antibodies that blockthese growth signals may help prevent a tumorfrom developing a blood supply, so that it remainssmall. The monoclonal antibody bevacizumabintercepts vascular endothelial growth factor(VEGF) and stops them from connecting withtheir targets.

TYPES OF CANCER

There are many different kind of cancer diverse by the type of cell that made up the tumor and therefore the tumor is known as the origin of cancer.

• Benign Tumor: A benign tumor is a lump of abnormal cells that do not spread to other cells or other parts of the body, but rather remains at the original location that it was formed.
• Malignant Tumor: A malignant tumor is a more dangerous form because it is able to invade and damage the functions of other cells and organs.

1. When cancers are derived from the epithelial cells whose genome has altered or damaged, we called it Carcinoma. It is the most common type of cancer occurring in humans and it begins in a tissue that lines the inner or outer surfaces of the body. The cells will begin to exhibit abnormal malignant properties. The most common example is the breast, lung, prostate cancers.
2. The second type is called Sarcoma which the cancers are arising from the connective tissue. It develops develop from cells originating in mesenchymal cells outside the bone marrow. Therefore Sarcoma includes tumors of bone (osteosacrcoma), fat (liposacrcoma), muscle (leiomyosarcoma) and vascular. There are two classes of cancer arise from the blood forming cells.
3. Leukemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of white blood cell. The cause of such cancer is also by mutation in the DNA that can trigger leukemia by activating oncogenes or deactivating tumor suppressor genes.
4. Lymphoma is a cancer that develops in the immune system. It usually presents to be a solid tumor in the lymphoid cells. The malignant cells often originate in the lymph node and presents as an enlargement of a tumor. It will also affect other organs such as skin, brain, bowels and bone.
5. Cancer also appears in the pluripotent cell in the testicle or the ovary. This is called the germ cell tumor. There are two types of germ cell tumor either cancerous or non-cancerous. It may cause by error in development of the embryo.
6. The last type is the Blastoma which is developed from immature embryonic tissue. This is most common in children.

SYMPTOM OF CANCER

• Uncontrolled Cell Division Cancer cells ignore signals that would regulate cell growth and division in the body. Since the cells grow and divide uncontrollably, it leads to the production of more and more cancer cells within the body.
• Evading Apoptosis Cancer cells are able to avoid the process of apoptosis for normal cells. Apoptosis is the process of programmed death carried out in normal cells, but cancer cells are able to evade the process and can therefore continue to progress.
• Independent from Growth Regulation Cancer cells are self-sufficient and do not require external signals to regulate its growth and division. Cancer cells are also capable of ignoring negative signals from its neighbors and can therefore continue to grow and divide on its own.
• Angiogenic The cancer cells that make up the tumor need a system to provide nutrients and dispose of waste. Therefore cancer cells have become angiogenic, in which the tumor attracts blood vessels to grow into the tumor mass and nourish the cancer cells.
• Immortality Cancer cells have developed the ability to proliferate indefinitely. By doing so, cancer cells have become immortalized and are capable of indefinite growth and cell division.
• Invasion and Metastasis Cancer cells are capable of entering the stage of metastasis and invade surrounding cells and tissues. By developing the ability invade and metastasize, cancer cells are able to spread and establish the disease in other areas of the body and not just the original location.

CAUSES

1. Viruses

In 1910, an American researcher, Peyton Rous, discovered that the Rous sarcoma virus (Rous virus)could cause cancer and he studied how this cancer could spread in chickens. He performed three experiment to test how this cancer spread.

1. He took out cancerous cells from one chicken and injected into a healthy chicken. He observed that the healthy chicken became afflicted with cancer.
2. He purified the cell to create cell-free extracts. He then injected the extract into a healthy chicken. Again, the chicken contracted cancer.
3. He used a special filter, that had holes too small for viruses to pass through, to filter the cells. He inject this extract into healthy chickens and discovered that they did not contract cancer, and remained healthy.

From his experiments, he concluded that viruses can cause cancer. Later, scientists discovered that the Rous virus is a retro-virus. A retro-virus can insert its gene into a host DNA and uses host protein mechanisms to reproduce. The viral DNA inside of the host cell causes uncontrollable cell division, cell growth, etc.

ONCOGENES

Oncogenes are genes that have the potential to cause tumors.

Classification

Although there are several different systems for classifying the oncogenes, these classifications are yet to be accepted standard. Some are grouped spatially or chronologically. The first category, growth factors (mitogen), include cancer genes such as fibrosarcomas, osteosarcomas, breast carcinomas, and melanomas. These genes induce cell proliferation. The growth factors from specific cells trigger cell proliferation not only in themselves but also nearby and distant cells. The Receptor tyrosine kinases cause breast cancer, non-small-cell lung cancer and pancreatic cancer. These receptor tyrosine kinases genes transduce signals for cell growth. The receptor tyrosine kinases add phosphate groups to other proteins. This can either turn the proteins permanently on or off. The cytoplasmic tyrosine kinases category include breast cancers, melanomas, ovarian cancers, head and neck cancers, blood cancers and brain cancers. These genes are in charge of the responses back and forth from active receptors of the cells that mediate proliferation, migration, differentiation and survival. The cytoplasmic serine/threonine kinases are responsible for malignant melanoma, colorectal cancer, and ovarian cancer. These genes are involves in cell cycle regulation, cell proliferation, cell survival, and apoptosis. More than 125 of the human protein kinases are serine/threonine kinases. The regulatory GTPases genes are involved in leading pathways to cell proliferation. An example of the regulatory GTPases include the Ras protein. The Ras hydrolyses GTP into GDP and phosphate and is responsible for adenocarcinomas of the pancreas and colon, thyroid tumors, and myeloid leukemia. Lastly, the transcription factors regulate the transcription of genes that trigger cell proliferation. For example, the myc gene can cause cancers such as small cell lung cancer, breast cancer, acute myeloid leukemia and malignant T-cell lymphomas (Souza et al., 2009).

CANCER DIAGNOSIS

Cancer cannot be diagnosed accurately by one single test. A complete and thorough history and physical examination along with several diagnostic tests must be performed in order to evaluate whether the patient has cancer or other conditions are being misinterpreted as symptoms of cancer.

An effective procedure of testing can be used to confirm or exclude the presence of cancer, determine the disease process and preliminary plan for treatments. Tests needed to be repeated if the patient’s symptoms have changed or the testing sample is not qualified or the test results show abnormality (Souza et al., 2009).

Diagnostic procedures for cancer may include imaging, laboratory tests, tumor biopsy, and endoscopic examination.

DIAGNOSTIC IMAGING

Diagnostic imaging is the process of obtaining pictures of body structures and organs. It is used to detect tumors and other abnormalities and their extent. It is also the most applicable way to determine the effectiveness of the treatments.

• Transmission imagingIn transmission imaging, a beam of photons with high energy is generated and allowed to pass through the body structure being examined.
• X-ray X-rays use electromagnetic energy beams to produce images of internal tissues, bones, and organs on film. Based on the images, tumor or cancer cells can be located.
• Computed Tomography scan (CT scan or CAT scan) A CT scan is more detailed than general X-ray scan. By combining x-rays and computer technology, images of bones, muscles, fat, and organs in the body are showed with more details.
• Bone scan Bone scans are pictures of X-ray or CT scan taken of the bone after a dye has been injected to bone tissue. These scans are used to detect tumors and abnormalities in the bone structure.
• Lymphangiogram(LAG)Lymphangiogram is an image that can detect cancer cells or abnormalities in the lymphatic system and structures after a dye is injected into the lymph system.
• Mammogram A mammogram is an x-ray image of the breast. It is used to detect and diagnose breast disease in women by locating abnormal area. A biopsy is required for further diagnosis.
• Reflection Imaging In Reflection Imaging, images are produced by high-frequency sounds bouncing off of the surface of body tissues and structures at varying speeds, depending on the density of the tissues present. The bounced sound waves are then analyzed by a computer and a visual image is produced.
• Emission Imaging MRI combine a large magnet and a computer to produce detailed images of the heart, brain, liver, pancreas, male and female reproductive organs, and other soft tissues.

LABORATORY TESTS

• Blood Tests Blood tests are used to check the levels of substances that are indicative of how healthy the body is and whether infection is present. Other tests check for the presence of electrolytes such as sodium and potassium that are critical to the body’s healthy functioning.
• UrinalysisUrinalysis breaks down the components of urine to check for the presence of drugs, blood, protein, and other substances.
• Tumor markers Tumor markers are substances released by cancer cells or substances created by the body in response to cancer cells.

Prostate-specific Antigen (PSA) An elevated PSA level in the blood may indicate prostate cancer, but other conditions such as benign prostatic hyperplasia (BPH) and prostatitis can also raise PSA levels.

CA 125 Ovarian cancer is the most common cause of elevated CA 125, but cancers of the uterus, cervix, pancreas, liver, colon, breast, lung, and digestive tract can also raise CA 125 levels.

Prostatic acid phosphatase (PAP) In addition to prostate cancer, elevated levels of PAP may indicate testicular cancer, leukemia, and non-Hodgkin’s lymphoma, as well as some noncancerous conditions.

Human chorionic gonadotropin (HCG)If pregnancy is ruled out, HCG may indicate cancer in the testis, ovary, liver, stomach, pancreas, and lung.

Carcinoembryonic Antigen (CEA) Colorectal cancer is the most common cancer that raises this tumor marker. Several other cancers can also raise levels of carcinoembryonic antigen.

Alpha-fetoprotein (AFP) In men, and in women who are not pregnant, an elevated level of AFP may indicate liver cancer or cancer of the ovary or testicle. Noncancerous conditions may also cause elevated AFP levels.

CA 19-9 Elevated levels of CA 19-9 may indicate advanced cancer in the pancreas, but it is also associated with noncancerous conditions, including gallstones, pancreatitis, cirrhosis of the liver.

CA 27-29 Cancers of the colon, stomach, kidney, lung, ovary, pancreas, uterus, and liver may also raise CA 27-29 levels. Noncancerous conditions associated with this substance are first trimester pregnancy, endometriosis, ovarian cysts, benign breast disease, kidney disease, and liver disease.

CA 15-3 Elevated levels of CA 15-3 are also associated with cancers of the ovary, lung, and prostate, as well as noncancerous conditions such as benign breast or ovarian disease, endometriosis, pelvic inflammatory disease, and hepatitis. Pregnancy and lactation also can raise CA 15-3 levels.

Neuron-specific enolase (NSE) NSE is associated with several cancers, but it is used most often to monitor treatment in patients with neuroblastoma or small cell lung cancer.

Tumor Biopsy

A biopsy is the removal of tissues or cells from the patient’s body for examination under a microscope. Biopsies are usually performed to determine whether a tumor is cancerous or just an infection or inflammation.

• Endoscopic biopsyThis type of biopsy is performed through a fiberoptic endoscope (a long, thin tube that has a close-focusing telescope at the end for closeup observation) through a natural body orifice or a small incision. The endoscope is used to view the organ in question for abnormal or suspicious areas, in order to obtain a small amount of tissue for study.
• Bone marrow biopsyThis type of biopsy is performed either from the sternum or the iliac crest hipbone. A needle is inserted into the marrow, and cells are taken for study.
• Excisional biopsyThis type of biopsy is often used when a wider or deeper portion of the skin is needed. Using a scalpel, a full thickness of skin is removed for further examination.
• Fine needle aspiration (FNA) biopsyThis type of biopsy involves using a thin needle to remove very small pieces from a tumor. FNA is not used for diagnosis of a suspicious mole, but may be used to biopsy large lymph nodes near a melanoma to see if the melanoma has metastasized (spread).
• Punch biopsy Punch biopsies involve taking a deeper sample of skin with a biopsy instrument that removes a short cylinder of tissue.
• Skin biopsy Skin biopsies involve removing a sample of skin for examination under the microscope to determine if melanoma is present.

ENDOSCOPIC EXAMINATIONS

An endoscope is a small, flexible tube with a light and a lens on the end used to look into the esophagus, stomach, duodenum, colon, or rectum. It can also be used to take tissue from the body for testing or to take color photographs of the inside of the body (Garraway, et al., 2005).

• Colonoscopy

Colonscopy involves inserting a colonoscope, which is a long, flexible, lighted tube, in through the rectum up into the colon. It allows the physician to view the entire length of the large intestine, and can often help identify abnormal growths as well as inflamed tissue, ulcers, and bleeding. The physician can also remove tissue for further examination.

• Endoscopic retrograde cholangiopancreatography (ERCP)

ERCP is a procedure that allows the physician to diagnose and treat problems in the liver, gallbladder, bile ducts, and pancreas. The procedure combines x-ray and the use of an endoscope. The scope is inserted through the patient’s mouth and throat, then through the esophagus, stomach, and duodenum.

• Esophagogastroduodenoscopy (EGD)

An EGD is a procedure that allows the physician to examine the inside of the esophagus, stomach, and duodenum. An endoscope is guided into the mouth and throat, then into the esophagus, stomach, and duodenum. The endoscope allows the physician to view the inside of this area of the body, as well as to insert instruments through a scope for the removal of a sample of tissue for biopsy.

• Sigmoidoscopy

A sigmoidoscopy is a diagnostic procedure that allows the physician to examine the inside of a portion of the large intestine, and is helpful in identifying the causes of diarrhea, abdominal pain, constipation, abnormal growths, and bleeding. A short, flexible, lighted tube, called a sigmoidoscope, is inserted into the intestine through the rectum. The scope blows air into the intestine to inflate it to have a better view of the inside.

• Cystoscopy

An examination in which a scope is inserted through the urethra to examine the bladder and urinary tract for structural abnormalities or obstructions, such as tumors or stones.

TREATMENT

Surgery

Surgery is one of the initial treatments used to operate on cancer cells. Cancer surgery attempts to prevent the spread of cancer cells by locating the tumor and removing it along with any possible lymph nodes that are near the source location. This method is commonly used for cases with benign tumors because the mass of cancer cells are typically located in one area. Surgery may be the only treatment needed for some cancer cases, but if a few cancer cells have broken off or get left behind, then it would only be a matter of time before the disease returns and more treatments are needed (Garraway, et al., 2005).

Chemotherapy

Chemotherapy is another treatment used in addition to surgery if cancer cells still remain in the body. Chemotherapy is used to treat cancer cells that have entered the stage of metastasis, in which the cells have spread from their original location. The treatment utilizes drugs that are toxic to interfere and kill cells that divide. The goal is to kill the cancer cells faster than the normal dividing cells in the body because cancer cells divide more rapidly. Even though chemotherapy has been proven to be effective, the side effects include hair loss and nausea because the treatment is blasting every cell being divided including the normal cells (Garraway, et al., 2000).

Radiation

Radiation therapy for cancer utilizes a beam of high-energy particles to kill off the cancer cells located in the body. This treatment targets the cancer areas by marking the skin, thus enabling the beam of high-energy particles to directly hit and destroy the cancer cells. The radiation from this therapy can shrink the tumors and also relieve the symptoms caused by the cancer. Although this therapy benefits cancer patients, it still has side effects and risks of causing new problems for these patients. The side effects caused by the radiation depends on the area of the body that undergoes the therapy; and this area is also the main location of the side effects.The radiation focuses on the tumor, but since the ray of high-energy particles targets the skin as well, a common side effect caused from radiation therapy is that the skin that was marked turns red and gradually may look more dark or tan over the years. The skin may also dry and flake, like a burn to the skin, during the period of recovery after the radiation therapy.

Monoclonal Antibodies

Monoclonal antibodies serve as a method in cancer therapy to enforce the immune system and aid in diagnosis. Monoclonal antibodies are created by injecting human cancer cells into mice so that they are able to produce antibodies against the foreign antigens invading their immune system. From there, the murine cells producing the antibodies are then removed and combined with laboratory-grown cells. This combination creates hybrid cells called hybridomas, which in turn is capable of producing large quantities of these pure antibodies so that the human body is able to process and use these antibodies to fight off the cancer cells.

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