How Do Thymidine Phosphorylase Inhibitors Work?

Thymidine phosphorylase inhibitors are a class of drugs used to treat colon (large intestine) or rectal cancer, gastric cancer, and esophageal cancer that has spread to other parts of the body in people who have already been treated with other chemotherapy medications or cannot receive chemotherapy medications.

Thymidine phosphorylase inhibitors work by inhibiting or blocking an enzyme called “thymidine phosphorylase,” a key enzyme in purine metabolism (chemical compounds that form uric acid when metabolized) and pyrimidine nucleoside salvage pathway. It catalyzes the reversible phosphorylation of thymidine and thereby generates thymine and 2-deoxy-D-ribose-1-phosphate. It is also identified as the angiogenic platelet-derived endothelial cell growth factor, which stimulates endothelial cell migration and angiogenesis (formation of new blood vessels) and plays an important role in tumor progression and metastasis.

This enzyme is expressed at higher levels in a wide variety of solid tumors than in the adjacent nonneoplastic tissues. Thymidine phosphorylase inhibitors suppress tumor growth by inhibiting this enzyme, increasing the proportion of apoptotic cells (a genetically regulated form of cell death) and to a certain extent inhibiting angiogenesis.

Thymidine phosphorylase inhibitors are administered via oral route.

Thymidine phosphorylase inhibitors work in the following ways:

• They belong to a class of medications called "thymidine-based nucleoside analogs" that work by stopping the growth of cancer cells. 
• In addition, they help in slowing the breakdown of trifluridine in the body.

Thymidine phosphorylase inhibitors are used to treat conditions such as:

• Metastatic colorectal cancer
• Gastric cancer
• Esophageal cancer

Some of the common side effects include:

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Tiredness/weakness
• Decreased appetite
• Mouth sores
• Stomatitis (inflammation of the mucus membrane of the mouth)
• Dysgeusia (a taste disorder that causes foul, rancid, metallic, or salty taste perception)

Other rare side effects include:

• Dizziness 
• Fatigue 
• Hair loss
• Rash/itching
• Anemia (low red blood cell count)
• Chills, sore throat, fever, or cough
• Thrombocytopenia (low blood platelet count)
• Pyrexia (fever)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of thymidine phosphorylase inhibitors include:

• Tipiracil/trifluridine
• Lonsurf