Development of Cancer

Development of Cancer 20/3/2008 1 CONTENT Introduction Oncogenesis Molecular basis of cancer Epidemiological causes of cancer Clinical assessment Investigation Therapies Prevention & screening Recent clinical trials Conclusion References. 20/3/2008 2 INTRODUCTION Cancer is a Latin word of ‘carcionos’. First Hippocrates, the father of medicine used the Greek words carcinos and carcinoma to describe the tumors. Cancer is a term for diseases in which normal cells divide without control and can invade other tissues. Spread: through the blood and lymph systems. 20/3/2008 3 Synonyms for malignant disease Synonym Neoplasia Tumour Definition New growth: Benign & malignant. Swelling: benign/inflammatory disease Carcinoma Sarcoma Leukaemia Malignancy of epithelial cell origin Malignancy of mesothelial cell origin Malignancy of white blood cells Lymphoma Malignancy of lymphoid organs 20/3/2008 4 Statistical analysis of cancer 20/3/2008 5 HISTORICAL PERSPECTIVE In 19th century: composed of aggregates of mucus or non-cellular matter. Otto Warburg proposed the combustion theory of cancer. Finally, Ames’ work on chemical mutagenesis convince that cancer originated through changes in DNA. In 1970s: Retroviruses study led to discover first human oncogene. 20/3/2008 6 Origin of cancer 20/3/2008 7 Mutation : Any permanent change in the DNA sequences. 20/3/2008 8 ONCOGENESIS STEP-1 STEP-2 20/3/2008 9 STEP-4 STEP-3 MOLECULAR BASIS OF CANCER Proto-oncogene 20/3/2008 10 Tumor suppressor gene 20/3/2008 11 Viral oncogene 20/3/2008 12 EPIDEMIOLOGICAL CAUSES OF CANCER DRUGS: Cytotoxics – Leukaemia. GENETICS: Breast cancer gene1/2 – breast & ovarian cancer. INFECTION: HPV-16 & 18 – cervical cancer. Adenopolyposis coil gene – colorectal cancer LIFE STYLE: OCCUPATIONAL: Asbestos - Meothelioma Aniline dyes – Bladder cancer. U.V. light – skin cancer. 20/3/2008 Tobacco – Lung, bladder, head & neck cancer. Alcohol – Oesophageal cancer. Aflatoxin – Liver cancer. 13 CLINICAL ASSESSMENT 1. LOCAL FEATURES OF MALIGNANT DISEASE SYMPTOM HAEMORRHAGE LUMP SITE/ TUMOUR STOMACH, COLON, BRONCHUS, BLADDER. BREAST, LYMPH NODE, TESTICLE. PAIN SKIN ABNORMALITY ULCER BONE. MELANOMA OESOPHAGUS, STOMACH, ANUS, SKIN. FRACTURE 20/3/2008 METASTATIC CANCER. 14 2. NON METASTATIC MANIFESTATIONS OF MALIGNANT DISEASE FEATURE WEIGHT LOSS, ANOREXIA FATIGUE HYPERCALCAEMIA COMMON ASSOCIATIONS GIT TUMOURS. ANY. MYELOMA, BREAST, RENAL TUMOURS. PROTHROMBOTIC TENDENCY NEUROPATHIES AND MYOPATHIES PANCREAS, GIT TUMOURS SMALL CELL LUNG CANCER. SKIN ABNORMALITIES GASTRIC, LUNG TUMOURS. 20/3/2008 15 INVESTIGATION Tumour marker: Tumor markers are substances produced by tumor cells or by other cells of the body in response to cancer or certain benign conditions. Found in the blood, in the urine, in the tumor tissue, or in other tissues. 20/3/2008 16 Example of tumor markers: TUMOR MARKERS Human chorionic gonadotropin. CA-125. Lactate dehydrogenase CANCER Gonadal germ cell tumor. Ovarian cancer, lymphomas. Lymphoma. NEO-PLASTIC CONDITION Pregnancy. Menstruation, pregnancy. Hepatitis, hemolytic anemia. 20/3/2008 17 Staging : is the determination of the extent of the malignancy. one of the most common system is: T- Tumour. N- Regional lymph nodes. M- Metastatic sites. 20/3/2008 18 TNM classification Extent of disease. T0 Excised tumor T1 T2 Increase in primary tumor size. T3 Increased involvement of nodes. N1 N2 Increase in involvement. N3 Presence of metastases. M0 Not present M1 Present 20/3/2008 19 THERAPIES 1.Surgery. 2. Radiotherapy. 3. Chemotherapy. 4. Biological therapy. 5. Novel and targeted therapies. 20/3/2008 20 1. SURGERY Most effective treatment method for cancer. About 40% of cancer patients are cured today by surgery. 20/3/2008 21 EXCISION 20/3/2008 22 PALLIATION 20/3/2008 23 2. RADIOTHERAPY Treatment of cancer with Ionising radiation. Delivered by 3 methods: 1.Teletherapy. 2. Brachytherapy. 3. I/V Injection of radioisotope. 20/3/2008 24 3. CHEMOTHERAPY Treatment that uses drugs to attack cancer cells. At present more than 50 anticancer drugs have been discovered. They are used in several ways: Monotherapy or only one drug Combination chemotherapy or a group of drugs which work together Combined modality or chemotherapy along with other treatment such as surgery and radiotherapy 20/3/2008 25 Commonly used cancer chemotherapy agents Alkylating agents: Cyclophosphamide, Mechlorethamine, Busulfan, Dacarbazine. Vinca alkaloids: Vinblastine, Vincristine. Antibiotics: Actinomycin D, Doxorubicin. Antimetabolites: Methotrexate, 6-mercaptopurine. Miscellaneous: Hydoxyurea, Procarbazine, Cisplatin. 26 20/3/2008 Hazards of chemo and radiotherapy 20/3/2008 27 TOXICITY AMELIORATION Condition 1.Bone marrow depression 2.Cystitis 3.Vomiting 4.Hyperuricaemia 5.Hypercalcaemia Drugs 1.Biological response modifiers like GM-CSF 2.mesna,acetylcysteine 3.Ondansetron 4.Allopurinol 5.Biophosphonates I/V 20/3/2008 28 4. BIOLOGICAL THERAPY 1) CYTOKINES: Involved such AS IL-1, IL-2,IL-4, IL-5, IL-12, GM-CSF IFN- α,IFN-β etc…. kidney & melanoma cancer. IFN- α : leukemia, lymphomas, & breast cancer. GM-CSF : melanoma cancer. IL-2 : 20/3/2008 29 2) IMMUNOTOXINS: are rich in protein & highly cytotoxic agents which produced by conjugating antibodies with highly toxic agents. Composed of MAbs coupled to lethal toxins & valuable for therapeutic reagents. Toxins like: Ricin, Shigella toxin, & Diphtheria toxin. Cure leukemia lymphoma & other types of cancers. 20/3/2008 30 5.NOVEL & TARGETED THERAPIES 1) MONOCLONAL ANTIBODIES: produced by a single type of cell & specific for particular antigen. production of anti-idiotype mabs used to treat b-cell lymphoma & t-cell leukemia cancer. 20/3/2008 31 short list of MAbs Oncolym and Zevalin: These are both Monoclonal antibodies with radioactive substances attached to the target proteins found only on the cancerous B cells in lymphoma. Rituxan MAbs: It is the first MAB to be approved in this country, & is effective against several forms of lymphoma cancer. Herceptin: This is effective in 20-30% of breast cancers. 20/3/2008 32 2) CANCER VACCINES: Vaccine is a preparation of antigenic material used to induce immunity again pathogenic organism. Used for infectious diseases like measles, mumps etc.. Designed to treat cancer or to prevent the development of cancer Therapeutic vaccines also diagnosed cancer. It stops growth of tumor & eliminate cancer cells. Used in treatment like: prostrate, ovary, kidney pancreases etc… 20/3/2008 33 Examples of cancer vaccines: Type of Cancer Cervical Cancer Vaccine Name GardasilTM HPV quadrivalent vaccine Lead Institution Merck & Co. Prostate Cancer Kidney Cancer GVAX® OncophageTM Cell Genesys, Inc Antigenics, Inc. 20/3/2008 34 PREVENTION OF CANCER 20/3/2008 35 SCREENING OF CANCER MALIGNANCY Breast cancer Cervical cancer Colorectal cancer Prostate cancer METHOD OF SCREENING Mamography Cervical smear cytology Sigmoidoscopy Serum prostrate Specific antigen BENIFITS Reduced mortality. Reduced mortality Possible reduced mortality Possible reduced mortality. 36 20/3/2008 RECENT CLINICAL TRIALS DRUG PHASE SPONSORE Ludwig Institute for Cancer Research New York NY-ESO-1 plasmid Phase I DNA CI-1040 Phase II National Cancer Institute 20/3/2008 37 CONCLUSION Cancer is a serious health issue that affects each and every one of us in some way, whether it is directly or indirectly. Most cases of cancer occur in the elderly because aging has an impact on cellular integrity; however, many heritable childhood cancers also exist. Finally, we would like to say that if we want to save our life then avoid things like, tobacco, fatty food, toxins etc…and eat regularly garlic olive leaf extract and Use herbs such as Echinacea, Astragalus, nutraceuticals and alkyglycerol to build your immune system which reduce the bacterial, viral, and fungal load on your immune system; and do exercise regularly, remove stress by doing meditation and prayer. 20/3/2008 38 REFERENCES USEFUL BOOKS: Harrison’s principles of internal medicine,16th edition,vol-1,oncology & hematology,(435-565). Davidson’s principles & practice of medicines,20th edition,Oncology(253271). K.D.Tripathi, essential of medical pharmacology,6th edition, anti-cancer drug,(819-834). Kuby,J., Immunology (5th edition)2000,(223-258). USEFUL WEBSITE: http://www.oncolink.upenn.edu. http://wwwcancer.org. http://wwwclinicaltrial.gov http://wwwindiacancer.org. 20/3/2008 39 THANK YOU… 20/3/2008 40