How Do Antineoplastic JAK Inhibitors Work?

Antineoplastic janus kinase (JAK) inhibitors are medications used to treat certain types of blood cancers and acute graft-versus-host-disease that can occur after stem cell transplant. Neoplasms are the abnormal growth of cells that may be benign or malignant and antineoplastics prevent, slow down or halt the growth of neoplasms.

JAK inhibitors are synthetic small molecule drugs that block the activity of enzymes known as Janus kinases, and their signaling pathways. Small molecule drugs are microscopic particles that can get inside a cell and change the way it functions.

Janus kinases are a group of enzymes known as protein tyrosine kinases that regulate the biological activity of proteins. Janus kinases are intracellular enzymes that transmit signals from the cell membrane downstream within the cell. There are four types of Janus kinases, JAK1, JAK2, JAK3 and tyrosine kinase (TYK2).

Janus kinases play a central role in the production and secretion of growth factors essential for blood cell formation (hematopoiesis), immune response, and cell cycle processes which involve cell growth, division, differentiation into specialized cells and programmed death.

Dysregulation of JAK signaling causes abnormal growth of blood cells in the bone marrow resulting in certain types of blood cancers. Unregulated JAK signaling after a stem cell transplant can cause an abnormal immune response and stimulate the immune cells to produce inflammatory proteins (cytokines), leading to acute inflammation.

JAK inhibitors slow down the progression of these conditions by interrupting the transmission of intracellular signals. JAK inhibitors work by blocking the activity of JAK2 or both JAK1 and JAK2, which mediate the signaling of a number of growth factors and cytokines that are important for hematopoiesis and immune function.

Antineoplastic JAK inhibitors are administered orally as tablets or capsules to treat the following conditions:

• Myelofibrosis: A bone marrow cancer in which mutations in hematopoietic stem cells cause uncontrolled growth of immature cells. The abnormal cells eventually develop into fibrous scar tissue and replace the normal soft, spongy tissue in the bone marrow and impair its ability to make healthy blood cells.
• Polycythemia vera: A rare type of blood cancer in which the bone marrow produces too many red cells.
• Acute graft-versus-host disease (GVHD): A complication that can occur after bone marrow or stem cell transplant, in which the transplanted donor stem cell derived immune cells attack the host cells such as skin, liver or the gastrointestinal tract.

Side effects of antineoplastic JAK inhibitors may include the following:

• Diarrhea
• Nausea
• Anemia
• Increase in blood creatinine
• Thrombocytopenia (low platelet count)
• Increase in liver enzymes:
  • Aspartate transaminase (AST)
  • Alanine transaminase (ALT)
• Vomiting
• Increase in the blood level of lipase, an enzyme that helps digest fats
• Increase in the blood level of amylase, an enzyme that breaks down starch
• Increase in cholesterol levels
• Increase in triglyceride levels
• Hyponatremia (low sodium level in the blood)
• Neutropenia (low count of neutrophils, a type of immune cells)
• Infections
• Edema
• Hemorrhage
• Bruising
• Dizziness
• Headache
• Fatigue or asthenia (weakness)
• Muscle spasms
• Pain in extremities
• Bone pain
• Weight gain
• Flatulence
• Herpes zoster
• Urinary tract infection
• Dysuria (painful or difficult urination)
• Hypertension (high blood pressure)

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 antineoplastic JAK inhibitors include:

• fedratinib
• Inrebic
• Jakafi
• ruxolitinib