Human Epidermal Growth Factor Receptor (HER) Signaling and Cancer Therapy
Human epidermal growth factor receptors (HERs) are receptors found on the surface of many cells in the body. As binding agents, they are integral to a number of healthy cell functions, including cell growth, programmed cell death (apoptosis) and the growth of new blood vessels (angiogenesis).
An over-expression of growth factor receptors has been identified as a contributing cause of tumor growth for several types of cancers. These include lung cancer, breast cancer, colon cancer and glioblastoma multiforme (brain tumor).
Due to the important role of growth factor receptors in these types of cancers, many researchers have targeted HERs as a potential avenue for cancer therapy. By reducing HER expression, the goal is to minimize proliferation of cancerous cells, program cancerous cells for death and/or cut off oxygen supply to the tumor by limiting the growth of new blood vessels.
Understanding Growth Factor Receptor Function
HERs initiate several cell activities through a process called dimerization. This process occurs when two receptor molecules bind in response to a growth factor molecule. These growth factor molecules are called ligands.
Four distinct HER proteins have been identified – HER1, HER2, HER3 and HER4. Signaling associated with each protein may lead to distinct intracellular activities. Similarly, the over-expression of specific proteins has been associated with specific forms of cancer. For example, an overabundance of HER2 is present in 20 to 30 percent of breast cancer patients. These patients typically have a poorer prognosis. It is for this reason that cancer medications geared towards halting HER over-production is seen as a promising subject of study.
History of HER Cancer Research
The HER signaling network has been extensively studied for the past few decades. During the 1980s, gene mapping and cloning of these cell surface components indicated that HER2 shared a similar structure to a mutated gene structure known to cause caner in birds. This fact formed the initial clue that would eventually link growth factor receptors to cancer proliferation.
Disrupting Accelerated Growth Factor Receptor Production
All HER chemotherapy drugs seek to limit downstream cell processes initiated by growth factor receptors. This may be achieved through a number of processes, such as blocking initial ligand binding through the use of monoclonal antibodies, or short-circuiting the actual intracellular signaling process via the use of small molecule inhibitors.
Current Cancer Drugs that Target HER Function
The Food & Drug Administration (FDA) has already approved a number of chemotherapy drugs that directly target HER function. These drugs may be used alone or in conjunction with other cancer drugs. The most common of these medications, along with their targeted cancer type, are listed below:
* Cetuximab (Erbitux): colon cancer
* Erlotinib (Tarceva): lung cancer
* Gefitinib (Iressa): lung cancer
* Panitumumab (Vectibix): colorectal cancer
* Trastuzumab: breast cancer
* Lapatinib: breast cancer
For these drugs to be prescribed, an increased production of growth factor receptors must be present in the patient’s body. This over-expression of HER suggests a poor response to traditional treatment medications. As such, HER function must be slowed or otherwise deterred (via these medications) to improve prognosis.
HER Chemotherapy Drugs Currently in Clinical Trials
Several other HER-targeting drugs are currently undergoing clinical trials. Depending the safety and effectiveness of these drugs, they may be approved for public use in the near future. Some of the more promising experimental HER drugs include:
* Matuzumab: colorectal cancer, lung cancer and stomach cancer
* Nimotuzumab: squamous cell carcinoma, head and neck cancer, nasopharyngeal cancer and glioma
* Zalutumumab: head and neck cancer
Sources for information on this page: Genentech (biooncology.com), American Association for Cancer Research