Vismodegib (trade name Erivedge ) is a drug for the treatment of

basal-cell carcinoma Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raise ...

(BCC). The approval of vismodegib on January 30, 2012, represents the first

Hedgehog signaling pathway The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper cell differentiation. Different parts of the embryo have different concentrations of hedgehog signaling proteins. The pathwa ...

targeting agent to gain U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) approval. The drug is also undergoing clinical trials for metastatic colorectal cancer,

small-cell lung cancer Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell c ...

, advanced stomach cancer, pancreatic cancer,

medulloblastoma Medulloblastoma is a common type of primary brain cancer in children. It originates in the part of the brain that is towards the back and the bottom, on the floor of the skull, in the cerebellum, or posterior fossa. The brain is divided into two ...

and

chondrosarcoma Chondrosarcoma is a bone sarcoma, a primary cancer composed of cells derived from transformed cells that produce cartilage. A chondrosarcoma is a member of a category of tumors of bone and soft tissue known as sarcomas. About 30% of bone sarcomas ...

. The drug was developed by the

biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...

pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field an ...

company Genentech.

Indication

Vismodegib is indicated for patients with

(BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation.

Mechanism of action

The substance acts as a

cyclopamine Cyclopamine (11-deoxojervine) is a naturally occurring chemical that belongs in the family of steroidal alkaloids. It is a teratogen isolated from the corn lily ('' Veratrum californicum'') that causes fatal birth defects. It prevents the embryo ...

-competitive antagonist of the

smoothened Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled (Class F) G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecula ...

receptor (SMO) which is part of the

. SMO inhibition causes the transcription factors

GLI1 Zinc finger protein GLI1 also known as glioma-associated oncogene is a protein that in humans is encoded by the GLI1 gene. It was originally isolated from human glioblastoma cells. Function The Gli proteins are the effectors of Hedgehog (Hh) ...

and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway. This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.

Side effects

In clinical trials, common

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s included gastrointestinal disorders (nausea, vomiting, diarrhoea, constipation), muscle spasms, fatigue, hair loss, and

dysgeusia Dysgeusia, also known as parageusia, is a distortion of the sense of taste. Dysgeusia is also often associated with ageusia, which is the complete lack of taste, and hypogeusia, which is a decrease in taste sensitivity. An alteration in taste or ...

(distortion of the sense of taste). The effects were mostly mild to moderate.

Development

Vismodegib has undergone several promising phase I and phase II clinical trials for its use in treating medulloblastoma.

References

External links

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Food and Drug Administration (FDA) approved vismodegib
{{Portal bar , Medicine Benzanilides Chloroarenes 2-Pyridyl compounds Benzosulfones Teratogens Antineoplastic drugs Hoffmann-La Roche brands Genentech brands