Cancer Chemotherapy-Duan

Question 1

What type of cancer chemo was used in the 1940s-1970s?

Answer 1

alkylating agents

**mustine (nitrogen mustard) used to treat Hodgkin’s lymphoma

Question 2

When did immunotherapy begin as a treatment option?

Answer 2

1990s

Question 3

What has cancer therapy been like in the 2000s?

Answer 3

biological cancer therapy

evolution of molecular oncology

Question 4

What are some of the differences b/w a normal cell & a cancer cell?

Answer 4

shorter (accelerated) cell cycle
excessive proliferation
higher activity of nucleic acid and protein synthesis
altered cell-cell communication
invasive (disrupt normal healthy tissues)
migration to distant sites - metastasis

Question 5

T/F Cancer cells use the same nutrients and metabolic process as normal host cells.

Answer 5

True.

Question 6

Describe the cell cycle briefly.

Answer 6

Go Resting Phase
G1 Presynthesis (Gap1)
S: DNA synthesis
G2: Pre-mitotic interval (Gap 2)
M: mitosis
G1

Question 7

What are Gaps 1 & 2 in the cell cycle?

Answer 7

Gap 1: G1 pre synthesis

Gap 2: G2 pre-mitotic interval

Question 8

What is a substance that can push a cell from Go to G1?

Answer 8

growth factor

Question 9

What does mitomycin C do? Which part of the cell cycle does it target?

Answer 9

• *cross links DNA & it is a bifunctional alkylate

* *targets G1

Question 10

What are some of the drugs that target S, the DNA synthesis phase? WHat is their main goal?

Answer 10

Main Goal: block DNA synthesis

DRugs: cytosine arabinoside, hydroxyurea, 6-MP, MTX, 5-FU,

Question 11

Which part of the cell cycle does etoposide target? What does it do?

Answer 11

Targets G2: DNA & protein synthesis

**inhibits topoisomerase II, causes DNA degradation

Question 12

Which drugs target the M phase of the cell cycle? What do they do?

Answer 12

Mechanism: block mitotic spindle formation
Drugs: vincristine, vinblastine, taxanes

Question 13

Give the 6 main classes of anticancer drugs.

Answer 13

1. alkylating agents
2. antimetabolites
3. antibiotics
4. hormones
5. nature products
6. miscellaneous

Question 14

What are the 3 categories of alkylating agents?

Answer 14

1. Nitrogen Mustards
2. Nitrosoureas
3. Alkyl Sulfonate

Question 15

Give 3 examples of nitrogen mustards.

Answer 15

Mechlorethamine
Cyclophosphamide
Ifosfamide

Question 16

Give 3 examples of nitrosoureas.

Answer 16

carmustine
lomustine
streptozotocin

Question 17

Generally speaking what do alkylating agents do?

Answer 17

interact with DNA nonspecifically

active even during Go

Question 18

What is the MOA of alkylating agents?

Answer 18

form covalent bonds with amino, carboxyl, sulfhydryl, and phosphate groups

Question 19

Which part of DNA is particularly susceptible to alkylation?

Answer 19

the electron rich nitrogen at the N7 position

Question 20

Why are nitrogen mustards toxic?

Answer 20

b/c they cross link DNA

Question 21

Describe specifically the MOA of nitrogen mustards.

Answer 21

chloroethyl side chains undergoes an intramolecular cyclization (Sn1) and forms carbonium ion intermediates or transition complex to become strong electrophiles
Nucleophilic attack of unstable aziridine ring by electron donor

Question 22

WHat are the results of the nitrogen mustards MOA?

Answer 22

enol tautomer favored
AT used instead of GC
imidazole ring opened
depurination
guanine residue excision
other 2-chloroethyl chain cyclized & 2 chains get cross linked!

Question 23

Which drugs cause cross linking between chains?

Answer 23

chlorambucil

melphalan

Question 24

What is a drug that causes cross linking w/i the same DNA strand?

Answer 24

cis-platinum

Question 25

What are the adverse reactions of nitrogen mustards?

Answer 25

teratogenic
immunosuppressive
carcinogenic

Question 26

What is the clinical use of nitrogen mustards?

Answer 26

lymphomas

leukemias