Cancer Chemotherapy-Duan Flashcards
What type of cancer chemo was used in the 1940s-1970s?
alkylating agents
**mustine (nitrogen mustard) used to treat Hodgkin’s lymphoma
When did immunotherapy begin as a treatment option?
1990s
What has cancer therapy been like in the 2000s?
biological cancer therapy
evolution of molecular oncology
What are some of the differences b/w a normal cell & a cancer cell?
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
T/F Cancer cells use the same nutrients and metabolic process as normal host cells.
True.
Describe the cell cycle briefly.
Go Resting Phase G1 Presynthesis (Gap1) S: DNA synthesis G2: Pre-mitotic interval (Gap 2) M: mitosis G1
What are Gaps 1 & 2 in the cell cycle?
Gap 1: G1 pre synthesis
Gap 2: G2 pre-mitotic interval
What is a substance that can push a cell from Go to G1?
growth factor
What does mitomycin C do? Which part of the cell cycle does it target?
- *cross links DNA & it is a bifunctional alkylate
* *targets G1
What are some of the drugs that target S, the DNA synthesis phase? WHat is their main goal?
Main Goal: block DNA synthesis
DRugs: cytosine arabinoside, hydroxyurea, 6-MP, MTX, 5-FU,
Which part of the cell cycle does etoposide target? What does it do?
Targets G2: DNA & protein synthesis
**inhibits topoisomerase II, causes DNA degradation
Which drugs target the M phase of the cell cycle? What do they do?
Mechanism: block mitotic spindle formation
Drugs: vincristine, vinblastine, taxanes
Give the 6 main classes of anticancer drugs.
- alkylating agents
- antimetabolites
- antibiotics
- hormones
- nature products
- miscellaneous
What are the 3 categories of alkylating agents?
- Nitrogen Mustards
- Nitrosoureas
- Alkyl Sulfonate
Give 3 examples of nitrogen mustards.
Mechlorethamine
Cyclophosphamide
Ifosfamide
Give 3 examples of nitrosoureas.
carmustine
lomustine
streptozotocin
Generally speaking what do alkylating agents do?
interact with DNA nonspecifically
active even during Go
What is the MOA of alkylating agents?
form covalent bonds with amino, carboxyl, sulfhydryl, and phosphate groups
Which part of DNA is particularly susceptible to alkylation?
the electron rich nitrogen at the N7 position
Why are nitrogen mustards toxic?
b/c they cross link DNA
Describe specifically the MOA of nitrogen mustards.
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
WHat are the results of the nitrogen mustards MOA?
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!
Which drugs cause cross linking between chains?
chlorambucil
melphalan
What is a drug that causes cross linking w/i the same DNA strand?
cis-platinum
