Alkylating agents
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most importantly, cyclophosphamide
mechanism of action
they damage DNA by attaching themselves to DNA—they alkylate DNA and cause DNA breaks
DNA repair enzymes are overwhelmed
DNA damage response leads to apoptosis in the presence of normal p53
this is cell-cycle-independent chemotherapy, so they are the mainstay of treatment for solid tumors
mechanism of resistance
decreased active drug uptake
mutant p53
overcome resistance by higher doses
toxicities
most importantly, highly mutagenic
wear gloves, don’t inhale them
must counsel re potential secondary cancers
Category: Pharmacology Notes
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