Step 1: Gemcitabine is infused as a prodrug; Step 2: Gemcitabine induces the cytoplasmic accumulation of HuR–dCK mRNA complexes (as well as the accumulation of HuR associated to other mRNAs, yet to be identified); Step 3: Activated and increased HuR enhances the expression of dCK (the enzyme that activates the prodrug gemcitabine), and proteins encoded by other HuR target mRNAs; Step 4: Gemcitabine (prodrug) is metabolized into active metabolites in cancer cells, in turn inhibiting the elongation of the DNA chain and causing cell death.
dCK: Deoxycytidine kinase.