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IHO Week 3 > Antineoplastics: General Concepts > Flashcards

Antineoplastics: General Concepts Flashcards

1
Q

What is the primary feature of cancer?

A

cancer alters DNA - either genetic or epigenetic

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2
Q

a typical definition of a “cure” is what?

A

5 years of disease-free survival

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3
Q

What is differential sensitivity in chemotherapy?

A

It’s the goal of eradicating the cancer cells WITHOUT affecting normal tissue

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4
Q

What are the 5 processes targeted by antineoplastic drugs?

A
  1. rapid cell growth (cytotoic drugs0
  2. angiogenesis/metastasis
  3. lack of differentiation - make them differentiate
  4. cell surface markers/lack of immune response
  5. defective gene products
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5
Q

Do we ahve drugs that correct th eunderlying defect for cancer?

A

No - we can’t fix the genetics yet

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6
Q

What are some cells affected by cytotoxic drugs?

A
  1. cancer cells
  2. bone marrow
  3. GI mucosa
  4. hai follicles
  5. taste buds
  6. cells that were previously irradiated
  7. fetus
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7
Q

What’s the dose-limiting side effect of the cytotoxic drugs?

A

bone marrow suppression - that’s why we give the drugs in cycles

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8
Q

IN order to reduce the impact of the recovery/resistance problems, what are three key principles of antineoplastic drug therapies?

A
  1. use high doses and dose escalation
  2. minimize recovery interval
  3. employ sequential scheduling during combination chemotherapy
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9
Q

Which will be less effetive at treating cancers with lowg rowth fractions: cell cycle specific or cell cycle nonspecific?

A

cell cycle specific - since they wont work on cells in G0

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10
Q

What are the two main classes of CCS drugs? What phases do they affect?

A
  1. plant alkaloids: G2-M

2. DNA synthesis inhibitors: S

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11
Q

Of the CCS and CCNS drugs, which is schedule dependent and which is dose dependent?

A

CCS - schedule dependent
CCNS - dose dependent
(sort of common sense)

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12
Q

What does the cell kill hypothesis propose?

A

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)

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13
Q

Can you stop treatment when symptoms resolve?

A

no! - you have to continue past the time when cancer cells can even be detected using conventional techniques

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14
Q

What are some factors of the cancer itself that will affect outcome?

A
  1. growth fraction (% not in G0)
  2. doubling time
  3. type
  4. stage
  5. resistance
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15
Q

What are some patient factors that will affect outcome?

A
  1. overall health - karnofsky scale
  2. bone marrow capacity
  3. liver function
  4. kidney function
  5. age
  6. compliance
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16
Q

What is the difference between primary resistance and acquired resistance?

A

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

17
Q

Does multidrug resistance occur after exposure to a single drug or multiple?

A

single (typically a natural product) drug

18
Q

WHat are some factors that will contribute to resistance?

A
  1. poor drug distribution
  2. sanctuary sites like the brain
  3. tumour cells not in cycle
  4. heterogeneity of tumor cells leading to clonal selection
19
Q

Mechanisms of resistance can be divided into what broad types?

A
  1. alterations that affect the mechanism of drug action

2. alterations that affect drug concentrations inside the tumor cell

20
Q

What are three examples of how a tumor cell can affect the drug’s mechanis of action?

A
  1. increase DNA repair
  2. form trapping agents
  3. change targt proteins (enzymes)
21
Q

What are three examples of how a tumor cell can affect the drug’ concentration in the cell?

A
  1. decrease activation of prodrugs
  2. increase inactivation
  3. decrease accumulation (by blocking transport in or increasing export out)
22
Q

What case of MDR is particularly problematic and why?

A

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

23
Q

Natural product MDR occurs from increased expression of what?

A
  1. P-glycoprotein (efflux pump)
  2. multidrug resistance proteins (MRP1-9)
  3. lung resistance protein

IHO Week 3 (10 decks)

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