3) Cancer.ppt

Dr. Inas Almazari Clinical Pharmacy Zarqa University  Introduction Cancer is the second leading cause of death in the United States Most common sites are the prostate, breast, lung and colon. Cancer can arise at any age (incidence  with age) Cancer is a dise...

Dr. Inas Almazari Clinical Pharmacy Zarqa University  Introduction Cancer is the second leading cause of death in the United States Most common sites are the prostate, breast, lung and colon. Cancer can arise at any age (incidence  with age) Cancer is a disease that results from abnormal growth and differentiation of tissues.  Cancer terminology The word “cancer” is from the Greek word for crab and reflects the finger-like projections that malignant tumors use to invade adjacent tissues. Malignant tumor cells may also produce growth factors that stimulate the formation of new blood vessels (a process called angiogenesis) that in turn support the rapid growth of tumor cells.  Cancer terminology Tumor or neoplasm: A mass of tissue in which the growth rate is excessive and uncoordinated when compared with normal tissues Benign neoplasm: Tumor cells that tend to be clustered in a single mass and are not malignant. Benign tumors usually will not cause death unless they interfere with vital function. Malignant neoplasm: tumors that have the ability to “metastasize” or break loose and spread to other areas of the body. Can cause great suffering and death if not treated. Specific names end with “oma.” For example, a hepatoma is a benign tumor of the liver, whereas a hepatocarcinoma would be a malignant tumor.  Specific nomenclature examples Carcinoma — Malignant tumor of epithelial cell origin. Sarcoma — Malignant tumor of skeletal or connective tissue origin. Lymphoma — Malignant tumor of lymphatic tissue. Glioma — Malignant tumor of the glial support cells in the central nervous system. Adenoma: benign tumor of glandular tissue. Adenocarcinoma: malignant tumor of glandular tissue  Metastasis The ability of tumor cells to spread (via blood or lymphatic vessels) to other parts of the body and establish secondary tumors. They enhance their potential for local invasion & metastatic spread by releasing protease enzymes that digest the extracellular matrix surrounding adjacent cells. Certain organs are prime locations for the formation of metastasis such as: – lungs due to the large amount of blood flow they receive from body. – liver for tumors originating in GIT because blood draining the intestines must first pass through the liver via the hepatic portal system.  Theories of oncogenesis Oncogenesis is the process by which normal cells are transformed into cancer cells. Abnormalities of tumor suppressor/inducer genes. Several proteins (such as p53 protein) limit cellular division by regulating parts of normal cell cycle. Failure of the anti- oncogenes (that suppress cell growth and code for these proteins) may lead to the unregulated cellular division that is characteristic of cancer cells. Excessive activity of proto-oncogenes (or a lack of their regulation) that produce proteins that enhance cellular growth and proliferation may cause excessive cellular division and growth.  Theories of oncogenesis 1.Mutation of DNA 2.Hereditary  Mutation of DNA.1 Numerous chemical, physical and biologic agents have been shown to be carcinogenic Many of these agents can damage cellular DNA, either directly or through production of toxic intermediates e.g. free radicals.  Mutation of DNA.1 Certain viruses are also oncogenic in that they may induce mutations in host cell DNA or alter rates of cellular transcription Mutations of cellular DNA can lead to the formation of cells with abnormal growth and differentiation patterns.  2. Hereditary  A genetic predisposition has been observed for a number of cancers including colon cancer, breast cancer, retinoblastoma and certain forms of leukemia and lymphoma.  A great deal of research has recently focused on identifying certain genetic markers in individuals that might pinpoint them as being at risk for the development of certain types of cancer.  Local effects of cancer Many cancers may be asymptomatic in the early stages. As the tumor(s) continue to grow, they have effects on local tissues as well as systemic effects on the body.  Compression of blood vessels  Ischemia  Pain  Bleeding  Infection  Altered tissue function  Systemic effects of cancer  Fatigue  Cachexia  Paraneoplastic syndrome  Bleeding and hemorrhage  Anemia due to chronic bleeding or bone marrow destruction (exacerbated by chemotherapy)  Altered organ function  Abnormal hormone production from an affected gland or directly from certain types of hormone- producing tumors  Cachexia A complex syndrome characterized by anorexia, weight loss and lean body (muscle) wasting seen in a significant percent of cancer and AIDS patients. A number of metabolic abnormalities that lead to poor utilization of nutrients and overall malnutrition. A key factor in cachexia is production of cytokines such as tumor necrosis factor and interleukins. These substances are protective against bacterial and viral infections as well as malignant cells. Unfortunately, these substances are responsible for many of the effects of cachexia including anorexia and lean body wasting.  PARANEOPLASTIC SYNDROME is a group of symptoms that may occur in patients with cancer that are distant to the site of the growing cancers. These symptoms are produced by substances released from the growing cancer cells and from cytokines released in response to the growing cancer.  PARANEOPLASTIC SYNDROME  Typical symptoms of paraneoplastic syndrome include: Dermatologic—itching, flushing, rashes Endocrine: – Cushing syndrome from tumor ACTH production – Water and electrolyte imbalance from tumor ADH release – Hypercalcemia due to PTH release by tumor cells. Neurologic: – Neuropathies – Lambert–Eaton syndrome—myasthenia-like syndrome associated with skeletal muscle weakness. Caused by IgG antibodies that attack motor neurons impair acetylcholine release in the neuromuscular junction. Rheumatologic—polyarthritis, polymyalgia  Tumor staging Tumors are staged by TNM system that includes a description of tumor size (T), involvement of lymph nodes (N) & metastasis (M).  Cancer detection Tumor cell markers Tumor grading Visualization Biopsy  Tumor cell markers Substances produced by or found on surface of tumor cells. Used clinically to screen for the presence of tumor cells in the body. Drawbacks to their use in cancer diagnosis: – May not be specific for a certain type of cancer – By the time tumor cell markers are detected, the particular cancer may be well progressed. – certain noncancerous conditions may be associated with the appearance of some of these markers in the blood.  Tumor grading Tumors may be examined microscopically to determine their degree of differentiation. The greater the degree of differentiation in a tumor, the more closely it will resemble its normal tissue. Tumors with a high degree on anaplasia are very poorly differentiated, do not resemble normal cells and tend to be very aggressive. The higher the degree of anaplasia a tumor exhibits, the poorer the prognosis. Tumors are grades on a scale from I to IV – I being more differentiated (less aggressive growth) – IV being the least differentiated (most aggressive growth)  Visualization X-rays, computer tomography (CT scans), magnetic resonance imaging Identifies the presence of a tumor or tumors; can also be used to evaluate metastasis Endoscopy may also be utilized to visually detect tumors in the bronchi and gastrointestinal tract  Biopsy Removal of a piece of suspect tissue for detailed histologic or histochemical analysis May be accomplished surgically, by a needle biopsy, by scraping cells from a surface (Pap smear) or by endoscopic biopsy  Rationale for cancer therapy To kill or arrest rapidly growing tumor cells. Can be multifaceted and may include: – surgical removal of tumors – Chemotherapy – radiation therapy A number of immune-based treatments are currently under investigation as alternatives to toxic chemotherapy and radiation therapy. Treatment with specific hormones has also been shown to inhibit the growth of certain types of cancers.  Rationale for cancer therapy Treatment of cancer Hormonal therapy Radiation therapy Immune-based therapies (“biologic response modifiers”)  Treatment of cancer Surgical removal of tumors is often a first step in treating cancer if the tumors are accessible and are isolated masses. Surgery is normally accompanied by chemotherapy or radiation therapy to kill any cancer cells that are not removed or have metastasized. Chemotherapy agents are drugs used to treat cancer. They fall into one of several general categories  Hormonal therapy Sex hormones are routinely used to inhibit tumor growth in breast, prostate and uterine cancer. The estrogen inhibitor tamoxifen may be effective in the treatment of breast cancer and may eventually be used as a prophylactic agent in women who are at a high risk for developing breast cancer. The androgen inhibitor flutamide has also been approved for treatment of prostate cancer.  Radiation therapy Utilizes ionizing or particle beam radiation to destroy cancer cells that are highly mitotic and most susceptible to the lethal effects of radiation. Localized & systemic side effects: alopecia, diarrhea, tissue irritation and organ inflammation.  Immune-based therapies (“biologic response modifiers”) Agents such as interferons, immunomodulators, tumor antigens & lymphokines/cytokines  means of enhancing the immune system response of individuals with cancer. Monoclonal antibodies are highly specific means of delivering chemotherapeutic drugs directly to cancer cells or as a means of blocking specific pathways in cancer cells that might be essential for replication or survival. Two monoclonal antibodies currently used: – bevacozumab (AvastinTM, an angiogenesis receptor inhibitor) – cetuximab (ErbituxTM, a growth factor receptor inhibitor).