Antineoplastics VI - Fitz Flashcards
What is the magic size of cancer cells that must have a blood supply in order to grow?
1-2 mm in diameter
Diffusion is no longer adequate to supply the cells with oxygen and nutrients and to take away wastes
How do most angiogenesis inhibitors work?
Interfering with the actions of substances that promote angiogenesis, particularly VEGF and mTOR
How do mTOR inhibitors work?
A serine/threonine kinase that reduces cell growth and proliferation, prevents angiogenesis and increases the cytotoxicity of drugs that damage DNA
What is Rebound Angiogenesis?
Rapid growth of cancer when an angiogenesis inhibitor is stopped
What is primary tumor suppression of angiogenesis elsewhere?
When a patient with a primary tumor only and no evidence of metastasis has the primary tumor removed and all of a sudden, metastasis occurs weeks later.
What is the mechanism of action for mTOR inhibitors?
Everolimus/Temsirolium
1) Reduces Cell Growth and Proliferation
- decreased cell cycle progression (cyclin D1 regulation)
- reduced bioenergetics (decreases access to nutrients)
2) Prevents Angiogenesis
3) Synergy with Drugs that Damage DNA
- prevents p21-mediated cell cycle arrest
How does Thalidomide work in Hansen’s Disease?
Suppressing Immune and Inflammatory Reactions
What is phocomelia?
A congenital malformation in which the hands and feet are attached to abbreviated arms and legs
What is the mechanism of action for Thalidomide?
Alters the ratios of various types of immune cells and changes in expression of molecular markers on their surface
Improves well-being and restores appetite and decreases wasting
Why are antineoplastic agents given in combination?
Decreased development of resistance, synergistic effects, and decreased toxic effects
What is pulse therapy?
intermittent treatment with very high doses of a drug, followed by drug-free periods to allow hematologic and immunologic recovery between treatment cycles
What drug is given in pulses?
Methotrexate to treat choriocarcinoma
What is rescue therapy?
Following the administration of toxic doses of chemotherapeutic agents for normal cells to be rescued by antidotes that only normal cells can use
What drug is give as a rescue therapy?
Leucovorin following high dose methotrexate treatment
What are the key principles of drug selection?
Active when used alone
Different MoAs or Chemical classes
CCNS vs. CCS or active in different stages of cell cycle
What results when appropriate drug selection has occurred?
- Synergistic Effects
- Decreased development of resistance
- Broader cell kill in cancers that consist of a heterogeneous tumor cell population
Define synergistic effects
Combined effect is greater than the sum of actions of individual drugs => lower doses => decreased toxicity
What is an example of drugs used together for synergistic effects?
Cytarabine + 6-Thioguanine
Define Recruitment
Use a CCNS drug to achieve significant log kill to cause cancer cells to re-enter the cell cycle, followed by administration of a CCS drug to kill the dividing cells
What is one example of a drug regimen that uses recruitment to treat breast cancer?
CMF (Cyclophosphamide, Methotrexate, 5-FU)
What is an example of drugs that use recruitment to treat AML?
Daunorubicin and Cytarabine
Define Synchrony
Use of CCS drugs to synchronize cells into simultaneous cell division so they are more sensitive to other drugs or radiation
What is an example of a drug that utilizes the concept of synchrony prior to administration of radiation?
Hydroxyurea
What is an example of an M phase drug that uses synchrony prior to the administration of another CCS S phase drug?
Vinca Alkaloids followed by Etoposide
