Cytarabine

CYTARABINE

Ferdinand F. Fatiga, RMT

CYTARABINE

• Used in the treatment of WBC cancers (AML/ALL) and Lymphoma

• Antimetabolite

• S-Phase-specific Chemotherapy drug

CYTARABINE

• Ara-C / Cytosine Arabinoside

CYTIDINE• Cytosine normally combines

with Ribose / Deoxyribose sugar

CYTARABINE vs. CYTIDINE

CYTARABINE (Mechanism of Action)

Nucleoside Transporter

dCK

Deoxycytidylate Kinase

NDK

Nucleotidase 1

CYTARABINE (Mechanism of Action)

MDR (P-glycoprotein)

CYTARABINE (Mechanism of Action)

Cytidine Deaminase

Deoxycytidylate Deaminase

CYTARABINE TRIPHOSPHATE

ACTION MODE OF araCTP

CYTARABINECytarabine is converted to its activated

Triphosphate form

Upon incorporation into DNA, the Cytidine analog interferes with chain elongation and promotes abnormal fragment ligation of newly synthesized DNA

If araCTP ends up being incorporated into DNA, it leads to Apoptosis

CONCLUSIONParameters in araC Sensitivity

Conversion to Triphosphate activated form by Kinases Inactivation via Deamination Overexpression of MDR transporters Half-life of active form araCTP

Increased expression of MDR such as P-glycoprotein and enzymes (Deaminases) that counteract the activation of araC to its activated araCTP cause cancer tumor cell resistance.

Thank you!