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23 Cards in this Set

  • Front
  • Back
What is the problem for cancer division?
Cancer cells fail to differentiate normally
What are the characteristics of cancer cells
1. Shift in control mechanisms that govern cell proliferation and differentiation, 2. proliferation in a dysregulated manner, 3. invasion of surrounding tissues -> secrets proteolytic enzymes, 4. metastesize, 5. fail to differentiate normally, 6. cell surface antigens, 7. enzymes, 8. oncogenes
What is the problem w/cancer clonoal origin?
There are subpopulation of cells within tumors that undergo repeated cycles of proliferation as to migrate to distant sites in the body to colonize various organs in the process called metastasis
What is the MOA for progressive selection of subclones?
Tumor stem cells have chromosomal abnormalities -> allows for more diversity in cell mutations
Cell cycle kinetics of cancer cells
1. Non-dividing and terminally differentiated (no genomic DNA replication), 2. cells that are continually proliferating, 3. cells that are resting but may be recruited into the cell cycle
What is the chemotherapeutic index(CTI)?
CTI = toxicity to cancer cells (lethal dose)/(toxicity to normal cells)
What is the objective of chemotherapy
To destroy the neoplastic cells via selective killing (selective toxicity) vs normal cells
What are the properties affecting tumor growth rate?
1. Proportion of actively dividing cells, 2. length of the cell cycle, 3. rate of cell loss
What does doubling time of a tumor depend on?
Exhibit a sigmoid-shaped growth curve -> varies w/tumor size
What is the goal of chemotherapy
Give drugs that can achieve a fractional cell kill in a log fashion (1-log kill = 90% of cell, 2-log kill =99%)
What is the way to increase chance of log kills?
Use combinations of agents w/differing toxicities and MOA thus can kill a variety of cells at once
What are locations of pharmacologic sanctuaries?
CNS, testes -> effective drug concentrations may be difficult to achieve
What is the problem of Cell cycle specific drugs (CCS)?
Tumor stem cells must also be in the sensitive phase of the cell cycle (ie not in Go)
What are the objectives of combination chemotherapy
1. Provides maximum cell kill within range of toxicity tolerated by host, 2. offers broader range of coverage of resistant cell lines in heterogenous tumor proliferation, 3. prevents or slows the development of new drug resistant cell lines
What are the drug dosing principles?
1. Use in combination, 2. make sure they do not share common mechanisms of resistance, 3. administer as frequently as possible, 4. do not have overlapping toxicities
What are the anti-cancer drugs that are susceptible to MDR-1 mediated resistance
1. Anthracyclines, 2. vinca alkaloids(vinblastine), 3. paclitaxel, 4. etoposide, 5. mitomycin, 6. plicamycin
What is primary resistance
Absence of response on the first exposure to currently available standard agents -> can be a form of acquired resistance
What gene and protein in cancer is related to drug efflux?
MDR1 gene -> produces cell surface glycoprotein (P-glycoprotein) -> causes chemtherapy drug efflux
What is the mechanism of resistance in MRP?
Multidrug resistance protein (MRP) -blocks the drugs from getting into the cell (ie resistance to anthracyclines + vinca alkaloids)
For what types of cancer do u use chemotherapy
For systemic cancers
What are the goals of chemotherapy
1. Control the spread, 2. cure, 3. palliative (if its gone too far)
What are the two types of antiemetics
1. Serotonin-receptor antagonists, 2. andidopaminergics
What drug is used to increase RBC count
Recombinant erythropoietin