How Do Hematologic Kinase Inhibitors Work?

Kinase inhibitors also known as tyrosine kinase inhibitors (TKIs) are potent anticancer drugs. They disrupt the signal transduction pathways of enzyme tyrosine kinases which are involved in cell growth, migration, differentiation, apoptosis, and cell death. These drugs are used for the treatment of patients with intermediate- or high-risk myelofibrosis (MF).

The JAK-STAT (Janus-associated kinase-signal transducer and activator of transcription) pathway plays a key role in the signaling of several cytokines and growth factors and is involved in cellular proliferation, growth, hematopoiesis, and the immune response. JAK kinase levels may be increased in inflammatory diseases, myeloproliferative disorders, and various malignancies.

Fedratinib acts as a competitive inhibitor of protein tyrosine kinase including JAK-2 and other related kinases: FLT3, CD135, STK1, FLK2, and RET. Fedratinib inhibits and blocks the cellular signaling (JAK-STAT), and thus, the proliferation of the tumor cells is suppressed and apoptosis (programmed cell death) may be induced.

Ruxolitinib specifically binds and inhibits protein tyrosine kinases JAK-1 and 2, thus reducing inflammation and inhibiting cellular proliferation.

Hematologic kinase inhibitors are used to treat:

• Myelofibrosis (myeloid cancer associated with anemia)
• Polycythemia vera
• Acute graft versus host disease

Side effects of hematologic kinase inhibitors may include:

• Diarrhea
• Nausea and vomiting
• Headache
• Dizziness
• Hypertension
• Anemia
• Thrombocytopenia
• Neutropenia
• Bone marrow hyperplasia
• Liver injury
• Increase in liver enzymes
• Increased blood creatinine
• Fatigue
• Muscle spasms
• Bacterial infections

The 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 hematologic kinase inhibitors include:

• Fedratinib (Inrebic)
• Ruxolitinib (Jakafi)