Drugs that disrupt DNA / Crosslinking agents / Resistance
I. Crosslinking agents
Common resistance mechanisms
(as a group; cancer cells may or may not develop resistance to an individual drug using one of these mechanisms)
-
increased production of nucleophilic substances (e.g., glutathione)
- increased DNA repair
- increased activity of repair enzymes (e.g., guanine O6-alkyl transferase)
- decreased activation (oral agents only)
- alkylating agents are susceptible to a form of multidrug resistance
- i.e., if you give one alkylating agent, and the cancer cells adapt by producing more glutathione or increasing DNA repair, the cancer cells will be less susceptible to other alkylating agents