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what is cancer?
- 1. loss of growth regulation
- 2. abnormal growth of cells
- 3. mutations in specific genes cause a normal cell to become cancerous
which genes are abnormal in cancer?
- genes that encourage the cell to multiply
- genes that stop the cell multiplying
- genes that repair the other damaged genes
what are carcinogens?
substances that cause cancer
what is oncology?
study of cancer
what is oncogene?
genes related to cancer
what are the 6 hallmarks of cancer?
- 1. self sufficiency in growth signals
- 2. insensitivity to antigrowth signals
- 3. tissue invasion and metastasis
- 4. limitless replicative potential
- 5. sustained angiogenesis
- 6. evading apoptosis
what is angiogenesis?
making new blood vessels
how do cancer cells reduce their dependence on growth signals from other cells?
- 1. produce their own extracellular growth factors
- 2. over express growth factor receptors
- 3. alterations to intracellular components of signaling pathways
how do cancer cells become insensitive to antigrowth signals?
disruption of retinoblastoma protein (pRB) pathway prevents inappropriate transition form the G1 phase of the cell cycle to the synthesis phase--> when this pathway is damaged, the cell can divide uncontrollably
how many checkpoints are there in the cell cycle?
how do cancer cells resist apoptosis?
mutation in any of the apoptosis pathways
how do cancer cells enable replicative immortality?
telomeres are maintained by telomerase allowing the cell to divide unlimited number of times
how do cancer cells induce angiogenesis?
the cells produce endothelial growth factor for angiogenesis
how do cancer Activate invasion and metastasis?
pioneer cells invade adjacent tissues and travel to other sites of the body where oxygen and nutrients are not limiting
what is extravasation?
get out of the blood vessels to start a new tumor
when is a tumor resistant to chemotherapy?
once it can metastasis
what are the 2 main types of cancer?
hematologic and carcinomas (solid tumors)
what are the 2 types of hematologic cancers?
leukemias and lymphomas
what are the 2 types of solid tumors?
carcinomas and sarcomas
what is leukemia cancer?
proliferation of immature committed WBC precursors which circulate in the blood
what is lymphoma cancer
cancer in the lymph system
what is carcinoma cancer?
originate in the epithelial cells
what is sarcoma cancer?
- originate in mesenchymal cells (embryonic connective tissue) develop in soft tissue parts
- i.e. cancer in connective tissue
what are the 4 ways of treating cancer?
- selective target therapy
what is the general mechanism of chemotherapy as treatment?
inhibition of DNA or destruction of DNA for rapidly dividing cells
what are antimetabolites?
type of chemo that interferes with DNA production and therefore cell division and the growth of tumors
what are the 3 types of antimetabolites?
- pyrimidine antimetabolites
- purine analogs
what is the mechanism of action of antifolates?
competes with folic acid for the enzyme dihydrofolate reductase DHFR and inhibits it so that there are less cofactors required for DNA synthesis
what is the mechanism of action of pyrimidine antimetabolites?
inhibits thymidylate synthetase the key enzyme in thymidylate synthesis. It also replaces uricil in RNA to something that doesn't work
what is the mechanism of action of purine analogs?
inhibit nucleotide and nucleic acid synthesis because it is incorporated into the nucleic acid
what is an example of an alkylating agent?
what is the mechanism of action of alkylating agents?
they form strong electrophiles through the formation of carbon ion intermediates --> formation of covalent linkages by alkylation of various nucleophiles moieties
what is the mechanism of alkaloid microtubule inhibitors?
used to block cells in mitosis by binding to tubulin
what can glucocorticoids do to treat cancer?
inhibitory effect of lymphocytes
what can estrogens do to treat cancer?
block the effect of androgen on androgen dependent prostate cancer
what can antiestrogens do to treat cancer?
competitive inhibitor of estradiol binding to the estrogen receptor in breast
what can androgen antagonists do to treat cancer?
inhibitor of androgen binding to androgen receptors for prostate cancer
what is the mechanism of platinum compounds in treating caner?
- platinum founds are DNA cross linking agents similar to alkylating agents
- the platinum compounds exchange chloride ions for nucleophilic groups of various kinds
what are the side effects of chemotherapy?
- 1. bone marrow suppression
- 2. digestive tract problems
- 3. alopecia
- 4. reproductive sterility
- 5. hyperuricemia - purines are degraded into uric acid
- 6. carcinogenesis
- 7. other drug specific toxicites
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