Biology - Cancer and Anti­ Cancer and Anti­ Cancer Drugs...

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Unformatted text preview: Cancer and Anti­ Cancer and Anti­ Cancer Drugs Cancer Cancer ► The oldest description of human cancer was found in an Egyptian papyrus about 2000 BC. The oldest specimen of a human cancer was found in a female skull ca 1600 BC. The skeletal remains of Peruvian Incas, ca 400 BC, contained lesions suggestive of malignant melanoma. ► Hippocrates was the first to recognize the difference between benign and malignant tumors . The swollen blood vessels around the malignant tumors so reminded him of crab claws, he called the disease karkinos (crab). ► Cancer is a class of diseases characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either directly or by implantation into distant sites by metastasis. Classification Classification ► ► ► ► ► ► Carcinoma: tumors derived from epithelial cells, including forms of breast, prostate, lung and colon cancer. Lymphoma and Leukemia: tumors derived from blood and bone marrow cells Sarcoma: tumors derived from connective tissue, or mesenchymal cells (from the embryonic mesoderm) Glioma: tumors derived from brain cells Germ cell tumors: tumors derived from germ cells, found in the testicle and ovary Choriocarcinoma: tumors derived from the placenta Cancer Statistics Cancer Statistics ► In 2008 7.6 million people died of cancer worldwide. ► The most common being: lung cancer stomach cancer liver cancer colorectal cancer breast cancer cancer is the leading cause of death. 2.6 million are diagnosed with cancer every year over half the men in China from smoke tobacco Lung cancer is the commonest form of cancer in China. Deaths from this disease have shot up fivefold since the 1970s ► In China Smoking and Lung Cancer Smoking and Lung Cancer ► Genetic Causes of Cancer Causes of Cancer ► Viral ►Herpes virus Kaposi sarcoma ►Human papilloma viruses Cervical cancer ►Retroviruses Feline leukemia ► Environmental ►Food: dietary factors; free radical genesis ►Air: cigarette smoke; asbestos ►Water: pesticides ►Radiation: X­rays, UV, Cosmic rays. Cancer Prevention Cancer Prevention ► Cancer is considered a largely preventable disease. Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: Tobacco usage Overweight/obesity Physical inactivity Alcohol over consumption Sexually transmitted infections (AIDS) Air pollution Other cases of cancer are caused through hereditary genetic disorders, and thus it is not possible to prevent all cases of cancer. Diet and Cancer Diet and Cancer ► The primary dietary factors that increase risk are obesity and alcohol consumption a diet low in fruits and vegetables high in red meat/and overzealous meat consumption Consumption of coffee is associated with a reduced risk of liver cancer. Studies have linked consumption of red or processed meat to an increased risk of breast cancer, colon cancer, and pancreatic cancer, a phenomenon which could be due to the presence of carcinogens in foods cooked at high temperatures. Characteristics of Cancer Cells • Cancer cells – Have abnormal nucleus – Lose normal control and divide indefinitely – They do not undergo apoptosis – They metastasize: spread to other areas – They promote the formation of new blood vessels (angiogenesis). – Telomeres do not shorten upon cell-division DNA REPLICATION DNA REPLICATION Antineoplastic Mechanisms Antineoplastic Mechanisms Transcription TRANSLATION Significance of the CellCycle in Cancer Significance of the Cell Cycle in Cancer Therapy ► Cell cycle Specific Agents Drugs effective at specific stages of growth: e.g . Bleomycin inhibits G2 ► Cell Cycle Non­ Specific Agents: Drugs that interfere at any interval in the cell cycle. ►Alkylating agents interfere with replication during all phase of the cell cycle. It is independent of the cycling. Cell Cycle Inhibition Cell VePesid 6­mercaptopurine Cell Cycle Inhibitors Cell Cell Cycle Inhibition Cell Cycle Inhibition Methotrexate/5­FU Nitrogen mustard/ Nitrosourea Doxorubicin/Dactinomycin Vinblastine/Vincristine Anti­Neoplastic Drug Classification….. Anti­Neoplastic Drug Classification….. ► Alkylating Agents Nitrogen mustard ► Cyclophosphamide Nitrosoureas ► Antimetabolites Folic Acid analog ► Methotrexate Pyrimidine analog ► Fluorouracil (5­FU) Purine analog ► Mercaptopurine (6­MP) Anti­Neoplastic Drug Classification Anti­Neoplastic Drug Classification ► Plant Alkaloids Vincristine Vinblastine VePecid-16 ► Antibiotics Dactinomycin ► Hormone analogs Tamoxifen (Antiestrogenic) Alkylating Agents Alkylating Agents Nitrogen mustards Defined by having two Defined choloro substituents on the same nitrogen. the They all have the They chloroalkyl group CH2CH2Cl. CH ► Targets Purine and pyridine bases in Purine DNA binding to C, O or N in the target molecule. the They form a crosslink within They the same DNA or between two the strands of DNA inhibiting separation of the DNA strands resulting in cell death. resulting Alkylating Agents Alkylating Agents ► Nitrogen Mustard Used to treat Hodgkin’s lymphoma*, lung, breast and ovarian cancer. ► Cyclophosphamide Administered orally. Toxic metabolites are known to affect the bladder and kidney. Used to treat leukemias, lymphomas and breast cancers. Hodgkin's disease, characterized by a particular cell known as the Reed-Sternberg cell. * Nitrosoureas Nitrosoureas ► ► ► ► This group also works by cross-linking proteins or nucleic acids. They are very lipophilic which enables them to cross the BBB and act against tumors of the CNS Because of their long-lasting effect on the WBC population they are administered every 68 weeks. Applied against lung, brain and gastrointestinal tumors. Adverse Effects Adverse Effects Anti­metabolites Anti­metabolites Synthetic analogs of nucleic acid bases resulting in an abnormal DNA ► ► ► ► ► Methotrexate is a folic acid analog which inhibits dihydrofolate reductase resulting in the stoppage of DNA synthesis. The drug is well absorbed either orally or intramuscularly. It crosses the BBB. High doses (0.2-20g) are sometimes required in cancer patients. The drug is used to treat sarcomas and breast cancer. Folate Metabolism Folate Metabolism DNA PURINES PURINES ► Adenine PYRIMIDINES ► Thymine ► Cytosine ► Guanine ► Uracil Mitotic inhibitors Mitotic inhibitors Vinca alkaloids ► Vincristine and vinblastine derived from the periwinkle plant. ► They bind to tubulin and inhibit spindle formation preventing the cells from undergoing mitosis (see fig). ► Both drugs are given intravenously and eliminated by hepatic biotransformation. ► Used in the treatment of breast cancer, testicular cancer, and sarcoma. ► Adverse reactions include bone marrow suppression and neuropathy. Mitosis Mitosis Periwinkle Periwinkle TAMOXIFEN:Hormone Analog TAMOXIFEN:Hormone Analog This is an anti-estrogen This analog. analog. ► It binds to the estrogen It receptor and inhibits DNA and RNA synthesis. DNA ► It decreases levels of It circulating prolactin, LH and FSH. and ► It is used extensively for It treatment of breast cancer. treatment Anti­estrogen Anti­estrogen Antineoplastic Agents: side effects Antineoplastic Agents: side effects Leukopenia, neutropenia, thrombocytopenia ► Blood clots (thrombosis), stroke ► Endometrial cancer, endometriosis ► Fertility issues ► Hair thinning ► Oral inflammation glossitis, xerostomia, stomatitis, teeth and gum sensitivity SUMMARY SUMMARY ...
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