Antineoplastics: General Concepts Flashcards
What is the primary feature of cancer?
cancer alters DNA - either genetic or epigenetic
a typical definition of a “cure” is what?
5 years of disease-free survival
What is differential sensitivity in chemotherapy?
It’s the goal of eradicating the cancer cells WITHOUT affecting normal tissue
What are the 5 processes targeted by antineoplastic drugs?
- rapid cell growth (cytotoic drugs0
- angiogenesis/metastasis
- lack of differentiation - make them differentiate
- cell surface markers/lack of immune response
- defective gene products
Do we ahve drugs that correct th eunderlying defect for cancer?
No - we can’t fix the genetics yet
What are some cells affected by cytotoxic drugs?
- cancer cells
- bone marrow
- GI mucosa
- hai follicles
- taste buds
- cells that were previously irradiated
- fetus
What’s the dose-limiting side effect of the cytotoxic drugs?
bone marrow suppression - that’s why we give the drugs in cycles
IN order to reduce the impact of the recovery/resistance problems, what are three key principles of antineoplastic drug therapies?
- use high doses and dose escalation
- minimize recovery interval
- employ sequential scheduling during combination chemotherapy
Which will be less effetive at treating cancers with lowg rowth fractions: cell cycle specific or cell cycle nonspecific?
cell cycle specific - since they wont work on cells in G0
What are the two main classes of CCS drugs? What phases do they affect?
- plant alkaloids: G2-M
2. DNA synthesis inhibitors: S
Of the CCS and CCNS drugs, which is schedule dependent and which is dose dependent?
CCS - schedule dependent
CCNS - dose dependent
(sort of common sense)
What does the cell kill hypothesis propose?
that actions of CCS drugs follow first order kinetics - so a given dose kills a constant PROPORTION of a tumor cell opoulation rather than a constant number of cells (works best for leukemias and lymphomas)
Can you stop treatment when symptoms resolve?
no! - you have to continue past the time when cancer cells can even be detected using conventional techniques
What are some factors of the cancer itself that will affect outcome?
- growth fraction (% not in G0)
- doubling time
- type
- stage
- resistance
What are some patient factors that will affect outcome?
- overall health - karnofsky scale
- bone marrow capacity
- liver function
- kidney function
- age
- compliance
What is the difference between primary resistance and acquired resistance?
primary resistance occurs when some inherent characteristic o the cancer cell prevenst the drug form working
acquired resistance occurs when cancer cells develop a resistance mutation during treatment
Does multidrug resistance occur after exposure to a single drug or multiple?
single (typically a natural product) drug
WHat are some factors that will contribute to resistance?
- poor drug distribution
- sanctuary sites like the brain
- tumour cells not in cycle
- heterogeneity of tumor cells leading to clonal selection
Mechanisms of resistance can be divided into what broad types?
- alterations that affect the mechanism of drug action
2. alterations that affect drug concentrations inside the tumor cell
What are three examples of how a tumor cell can affect the drug’s mechanis of action?
- increase DNA repair
- form trapping agents
- change targt proteins (enzymes)
What are three examples of how a tumor cell can affect the drug’ concentration in the cell?
- decrease activation of prodrugs
- increase inactivation
- decrease accumulation (by blocking transport in or increasing export out)
What case of MDR is particularly problematic and why?
Usually MDR occurs when you give one drug and resistance develops to the other drugs in that class, but there is an instanc e of MDR where resistance occurs to all natural products, which crosses mechanism classes
Natural product MDR occurs from increased expression of what?
- P-glycoprotein (efflux pump)
- multidrug resistance proteins (MRP1-9)
- lung resistance protein
