Lecture 24_Cancer III

Question 1

What are clonogenic cells?

Answer 1

They have the potential to produce progeny to such an extent that results in the death of the host.

Question 2

The goal of chemotherapy is to…

Answer 2

…kill all clonogenic cells.

Question 3

What is the fractional kill hypothesis?

Answer 3

• A constant fraction of cancer cells is killed by an antineoplastic drug per unit time.
• If a malignant tumor contains 10^12 cells, killing 99.99% of these cells with an antineoplastic drug (good enough for clinical remission) would still leave 10^8 cells that could regrow. A second treatment would again kill 99.99% of cells, leaving 10,000 cells.

Question 4

Some cancer chemotherapeutic drugs have very steep dose-response curves. What does this mean for treatment?

Answer 4

Most treatments are given at the highest tolerable dosages and bone marrow transplantation can be used if the antineoplastic drug dose used needs to be even higher.

Question 5

What’s the issue with tumors that grow in body compartments?

Answer 5

Chemotherapeutic agents have limited access. Local administration of drug may be necessary.

Question 6

Antineoplastic drugs

Answer 6

• Low therapeutic index
• Not at all specific in their actions
• Damage also occurs to other dividing tissues such as bone marrow, gonads, oral and gi mucosa, and hair follicles

Question 7

Doses and schedules of antineoplastic drug delivery

Answer 7

• Limited by tissue tolerance
• High-dose intermittent schedules are more effective than low dose daily administration
• Intermittent delivery allows for tissue recovery between treatment cyces

Question 8

Combination chemotherapy

Answer 8

• Works better than individually
• Best if each drug has different mechanism of action as well as qualitatively different toxicity (so each drug may be given at near its max tolerated dose).
• If a particular cell is resistant to one drug it will not likely be resistant to the other.

Question 9

Adjuvant chemotherapy

Answer 9

Admin of drugs to patients who show no evident signs of cancer but are at high risk of developing recurrent cancer (eg. tamoxifen after breast or colorectal cancer therapy).

Question 10

Combined-modality treatments

Answer 10

(from surgery, radiation and chemotherapy) are commonly used, and appear to be especially useful in the treatment of childhood cancers.

Question 11

Cytotoxic antineoplastic drugs

Answer 11

• Alkylating and DNA binding agents
• Antimetabolites
• Antibiotics
• Natural plant derivatives