How Do Antineoplastic Hedgehog Pathway Inhibitors Work?

Antineoplastic Hedgehog (Hh) pathway inhibitors are a class of drugs used to treat basal cell carcinoma (BCC; a type of skin cancer) that has recurred following surgery or radiation therapy and for those who are not candidates for surgery or radiation therapy and to treat acute myeloid leukemia (a cancer of the blood and bone marrow) in adults 75 years or older or who cannot use standard chemotherapy because of other medical conditions.

Hh pathway inhibitors are drugs designed to selectively inhibit abnormal signaling in the Hh pathway that plays an essential role in cell growth and differentiation in the developing embryo. In postembryonic life, the Hh pathway promotes cellular development and division in several cell types, both by direct cellular activation and secondary activation of multiple pathways of tissue generation, including angiogenesis (new blood vessel formation) and tissue growth.

The Hh pathway is typically over-activated in BCC through downregulation of Hh signal inhibition. The Hh pathway inhibitors bind to and inhibit Smoothened, a transmembrane protein involved in Hh signal transduction. This inhibition of the Hh signaling pathway can be a useful strategy for restricting tumor growth and preventing the recurrence of the disease postsurgery, postradiotherapy, or postchemotherapy.

Hh pathway inhibitors are administered orally once daily with or without food. 

Hh pathway inhibitors work in the following ways:

• They work by slowing down or stopping the growth of cancer cells.
• They bind to and inhibit Smoothened, a transmembrane protein involved in Hh signal transduction.
• This inhibition of the Hh signaling pathway helps to slow down the spread of cancer cells and may help shrink tumors.

Antineoplastic Hh inhibitors are used to treat conditions such as:

• Acute myeloid leukemia (cancer of the blood and bone marrow)
• Basal cell carcinoma (a type of skin cancer)

Some of the common side effects include:

• Nausea
• Vomiting
• Constipation
• Diarrhea
• Headache
• Altered taste sensation
• Tiredness/weakness
• Muscle/joint/back pain
• Loss of appetite
• Abdominal pain
• Other rare side effects include:
• Dizziness 
• Fatigue 
• Weight loss
• Hair loss
• Chest pain
• Anemia (low red blood cell count)
• Insomnia 
• Shortness of breath
• Chills, sore throat, fever, or cough
• Rash/hives/itching
• Thrombocytopenia (low blood platelet count)
• Easy bruising/bleeding
• Peripheral edema (swelling of lower legs or hands)
• Increased creatinine (a waste product formed by the normal breakdown of muscle cells)
• Missed menstrual periods
• Decreased urination
• Hyponatremia (low blood sodium level)
• Hyperglycemia (high blood glucose level)

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 Hh pathway inhibitors include:

• Daurismo
• Erivedge
• Glasdegib
• Odomzo
• Sonidegib
• Vismodegib