(2) Cell cycle nonspecific agents (CCNSA): Kill proliferating cells preferentially, act on cells at all phases. (3) Cell cycle specific agents (CCSA) Act at specific phase of the cell cycle
• (2) Cell cycle nonspecific agents (CCNSA): • Kill proliferating cells preferentially, act on cells at all phases. • (3) Cell cycle specific agents (CCSA): • Act at specific phase of the cell cycle
o Biochemic mechanism 1)Interfere nucleotide synthesis. 2)Impact the structure and function of DNA 3)Interfere transcription and block rNa synthesis 4) Interfere protein synthesis and functions 5) Change hormone lever
• Biochemic mechanism: • 1) Interfere nucleotide synthesis. • 2) Impact the structure and function of DNA • 3) Interfere transcription and block RNA synthesis. • 4) Interfere protein synthesis and functions. • 5) Change hormone lever
Resistance mechanism (1) Defective activation: Cyclophosphamide requires metabolic activation. Methotrexate conversion to more active mtx polyglutamate in cells
Resistance mechanism • (1) Defective activation: Cyclophosphamide requires metabolic activation, Methotrexate conversion to more active MTXpolyglutamate in cells
(2) Increased inactivation: e.g aldehyde dehydrogenase converse cyclophosphamide to inactive metabolite. (3) Altered nucleotide pools: Can occur with antimetabolites
• (2) Increased inactivation: e.g., aldehyde dehydrogenase converse cyclophosphamide to inactive metabolite. • (3) Altered nucleotide pools: Can occur with antimetabolites
(4) Altered DNA repair: Repair mechanisms increased, i.e., ability to remove cross-links Affect the action of bleomycin and other DNA-directed drugs (5) Altered target: Less affinity for drug, Methotrexate Dihydrofolate reductase changes )
• (4) Altered DNA repair: Repair mechanisms increased, i.e., ability to remove cross-links, Affect the action of bleomycin and other DNA-directed drugs • (5) Altered target: Less affinity for drug, Methotrexate (Dihydrofolate reductase changes )