Presentation on theme: "Antineoplastics W hat is Cancer ? Cancer is a disorder of cell division (leading cause of death). C C ancers most commonly occur in: breast (♀) -"— Presentation transcript:
Antineoplastics W hat is Cancer ? Cancer is a disorder of cell division (leading cause of death). C C ancers most commonly occur in: breast (♀) - prostate (♂) - lung - colon - rectum C ommon characteristics of neoplastic cells: - Persistent proliferation and Immortality -Dedifferentiation. - Invasive growth - Formation of metastases -Sustained angiogenesis.
Antineoplastics Cancer Etiology -The abnormal behavior of cancer cells results from DNA alterations. Malignant transformation results from a combination of activation of oncogenes and inactivation of tumor suppressor genes. - These genetic alterations are caused by: Chemical carcinogens (cigarette smoking). Pathogens (hepatitis C virus, H. pylori). Radiation (X-rays). Hereditary factors. Drugs (estrogen).
Antineoplastics T Treatment Modalities: 1.Surgery (solid tumors). 2. Radiation (solid tumors). 3. Drug therapy: -Disseminated cancers (leukemias, lymphomas & widespread metastases. -Some localized tumors e.g. testicular carcinoma. -Adjuvant to surgery & radiation.
Antineoplastics G Goals of therapy: - C ure e.g. Hodgkin ̕ s disease - Prophylaxis of recurrence - Prolong survival - Palliation of symptoms OOutcome of therapy depends on: - General health of patient -Responsiveness of cancer type (size, location, grade, etc.). -Drug resistance.
Antineoplastics Drug Selection Combination therapy is more effective than single drug therapy - maximal cell kill - ↓ Injury to normal cells. - slow/prevent development of drug resistant Criteria of drug selection for combination therapy - different MOAs (act at diff. cell-cycle stages) - different toxicities (↓overlapping toxicities) - Each drug effective by itself
Antineoplastics Tumor staging Most commonly applied staging system for solid tumors is TNM (tumor-nodes-metastases) classification where a numerical value is assigned to each letter to indicate size or disease extent. TNM system T: refers to the size of the primary tumor (0-4) e.g. T 4 (large size tumor). N: refers to the extent of lymph nodes involvement (0-4) e.g. N 0 (no lymph node disease). N x (Lymph nodes not assessed). M: refers to the presence or absence of distant metastasis (0-1) e.g. M 1 (distant metastasis). M 0 ( No distant metastasis). M x (distant metastasis not assessed). T 2 N 1 M 0 (moderate size tumor with limited nodal disease and no distant metastases).
Antineoplastics Growth Fraction = GF = Proliferating cells (S or M phase) /resting cells (G 0 ). Cell-cycle phase specific (phase specific) drugs Cell-cycle phase non-specific (cycle specific) drugs G 1 = 40% S = 39% G 2 = 19% M = 2% Checkpoints: P27: G 1 -S P53: G 2 -M
Antineoplastics Cell-Cycle Drug Effects 1. Cell-cycle phase-specific drugs: Must be present for an extended time → given by infusions or in frequent small doses. G1-phase specific: Asparaginase (Enzyme). S-phase specific: Methotrexate, Fluorouracil, Mercaptopurine (Antimetabolites). G2-phase specific: Bleomycin (Antitumor antibiotic) M-phase specific: Vinca alkaloids (Vincristine, Vinblastine) (Mitotic inhibitors).
Antineoplastics 2. Cell-cycle phase non-specific drugs (cycle- specific): Act during any phase including G0. More toxic to proliferating cells than G0 cells. cyclophosphamide. Carmustine: Alkylating agents. Cisplatin, Carboplatin: Platinium compds. Doxorubicin: Antitumor antibiotics.
Antineoplastics Unique toxicities A.Cardiotoxicity: Doxorubicin &.B. Nephrotoxicity: Cisplatin & Methotrexate. C. Pulmonary Toxicity: Bleomycin. D. Hepatotoxicity: Asparaginase E. Hemorrhagic cystitis: Cyclophosphamide → acrolein F. Neurotoxicity: Vincristine, Cisplatin.
Antineoplastics Estrogen Receptor Assay Progesterone Receptor Assay Lab test done to find out if cancer cells have estrogen (progesterone) receptors Lab testcancercellsestrogen (progesterone) receptors Cells with ERs need E to grow while cells with PRs need P to grow. ER + growth of cancer cells is E-dependant ER ¯ growth of cancer cells is E-independent
Antineoplastics Tumor markers Tumor markers are substances found in blood, urine and tissues, produced by tumor cells or by other body cells in response to cancer or certain benign conditions. An elevated level of a tumor marker can indicate cancer; however, there can also be other causes of the elevation. Tumor marker levels are checked at the time of diagnosis; before, during, and after therapy; and then periodically to monitor for recurrence.
Antineoplastics Tumor MarkerAssociated TumorCEA Carcinoembryonic Antigen GIT, BREAST, LUNG CANCERS CA-125 Cancer Antigen-125 OVARIAN CANCER OVARIAN CANCER PSA Prostate Specific Antigen PROSTATE CANCER β-HCG Human Chorionic Gonadropin TESTICULAR CANCER AFPAlpha-fetoprotein LIVER CANCER TgThyroglobulin THYROID CANCER
Antineoplastics If a man has ↑ PSA level Search for PC If a person has ↑ β-HCG level Search for testicular cancer If a person has ↑ AFP level Search for liver cancer
Antineoplastics M 0 means… No distant metastasis N x means… Lymph nodes not assessed M x means…. Distant metastasis not assessed