Cytotoxic nucleoside analogs--- such as cladribine, cytarabine, and gemcitabine--- are a class of antimetabolite anti-cancer drugs that block the last enzymatic step of DNA synthesis: DNA polymerase.
Cladribine a purine analog that is resistant to adenosine deaminase--- the enzyme in the purine disposal pathway that normally degrades purine analogs and adenosine--- allowing it to reach very high intracellular levels. Once phosphorylated to a triphosphate form, it can either get incorporated into DNA and cause breaks, or it can inhibit DNA polymerase alpha and beta and thus inhibit DNA synthesis and repair. As a result, the cell is arrested during the S phase. Cladribine is particularly effective in treating hairy cell leukemia, and can cause complete remission in patients. However, it has a tendency to induce myelosuppression, which leads to a prolonged decrease in T lymphocyte levels and increases the risk of infection.
Cytarabine is a pyrimidine analog and, unlike other pyrimidine analog antimetabolite drugs, does not affect the folate cycle. Instead, it is converted into a triphosphate metabolite that competitively inhibits DNA polymerase alpha and beta, thus preventing DNA synthesis and repair. Cytarabine is only active against hematologic malignancies including AML and non-Hodgkin lymphoma. Like cladribine, the main adverse effect of cytaribine is myelosuppression.
Gemcitabine is similar to cytarabine in that it is another pyrimidine analog that also inhibits DNA synthesis and repair. The mtabolites of gemcitabine can also cause chain termination and inhibit ribonucleotide reductase. Unlike cytaribine, however, gemcitabine is active against both hematologic malignancies and solid tumors, albeit it still can cause myelosuppression like the other drugs mentioned.
Cladribine is a cytotoxic purine analog that inhibits DNA polymerase and thus inhibits DNA synthesis and repair. It is used primarily to treat hairy cell leukemia.
Cladribine, cytarabine, and gemcitabine are antimetabolites that arrest the cell at the S phase of the cell cycle, which is the phase when DNA synthesis occurs. By disrupting this phase, these drugs inhibit the growth and reproduction of cancer cells.
Cytarabine and gemcitabine are both cytotoxic pyrimidine analogs that inhibit DNA polymerase and thus inhibit DNA synthesis and repair. However, they have different uses in treatment. Cytarabine is ONLY active against hematologic malignancies (such as AML and non-Hodgkin lymphoma), while gemcitabine is effective against BOTH hematologic malignancies and solid tumors.
Cladribine, cytarabine, and gemcitabine can cause myelosuppression, which is the reduction of bone marrow activity that leads to fewer red and white blood cells and platelets. They can also induce immunosuppression leading to an increased risk of infection in the patient.
All three drugs are designed to mimic the building blocks of DNA, known as nucleosides. They integrate themselves into the DNA molecules being synthesized, causing errors and disruptions. This cytotoxic action specifically targets rapidly dividing cells, like cancer cells, hence why they are referred as cytotoxic nucleoside analogs.