Targeted therapy

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List of terms related to Targeted therapy

Overview

Targeted therapy is a type of medication which blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with rapidly dividing cells. Targeted cancer therapies may be more effective than current treatments and less harmful to normal cells.

The main categories of targeted therapy are small molecules and monoclonal antibodies.

Small molecules

• Imatinib mesylate (Gleevec®, also known as STI–571) is approved for chronic myelogenous leukemia, gastrointestinal stromal tumor and some other types of cancer. Early clinical trials indicate that imatinib may be effective in treatment of dermatofibrosarcoma protuberans.
• Gefitinib (Iressa®, also known as ZD1839), targets the epidermal growth factor receptor (EGFR) tyrosine kinase and is approved in the U.S. for non small cell lung cancer. EGFR is also overexpressed in the cells of other solid tumors, such as lung and breast cancers. This leads to inappropriate activation of the apoptotic Ras signal transduction cascade, eventually leading to uncontrolled cell proliferation.Gefitinib inhibits EGFR tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited; and malignant cells are inhibited.
• Erlotinib (marketed as Tarceva). Erlotinib works through a similar mechanism as gefitinib. Erlotinib has been shown to increase survival in metastatic non small cell lung cancer when used as second line therapy. Because of this finding, erlotinib has replaced gefitinib in this setting.
• Bortezomib (Velcade®) is an apoptosis-inducing drug that causes cancer cells to undergo cell death by interfering with proteins. It is approved in the U.S. to treat multiple myeloma that has not responded to other treatments.

Monoclonal antibodies

Main article: Monoclonal antibody therapy

Several are in development and a few have been licenced by the FDA. Examples of licenced monoclonal antibodies include:

• Rituximab targets CD20 found on B cells. It is used in non Hodgkin lymphoma
• Trastuzumab (Herceptin®) targets the Her2/neu (also known as ErbB2) receptor expressed in some types of breast cancer
• Cetuximab (marketed as Erbitux) targets the epidermal growth factor receptor. It is used in the treatment of colon cancer.
• Bevacizumab (marketed as Avastin) targets circulating VEGF ligand. It is approved for use in the treatment of colon cancer and is investigational in the treatment of breast cancer and sarcoma

Progress and future

Many oncologists believe that targeted therapies are the chemotherapy of the future. As solid tumor cancer continues to be viewed as a chronic condition, methods for long-term treatment, with less side-effects, continue to be investigated.

In the U.S., the National Cancer Institute's Molecular Targets Development Program (MTDP) to identify and evaluate molecular targets that may be candidates for drug development.

The next stage of targeted therapies will focus on finding which patients will respond to which targeted therapies. This is called the identification of "sub-populations". The route to identify these sub-populations is through biomarkers and surrogate endpoints.

References

• Green, Mark Targeting Targeted Therapy New England Journal of Medicine (May 20, 2004)
• Molecular Oncology: Receptor-Based Therapy Journal of Clinical Oncology (April 10, 2005)
• Lynch, Thomas Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib New England Journal of Medicine (May 20, 2004)

See also

• Advances in Targeted Cancer Therapies
• National Cancer Institute Fact Sheet

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