Mass General Hospital Cancer Center treats patients with many cancer types. To learn more about the different cancer types that can be treated at the Cancer Center, please visit the Cancer Center website at the following page:
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ERBB3, often called HER3, is a gene that provides the code for making a cell surface protein called the ErbB3 (HER3) growth factor receptor. When certain growth factors (proteins that stimulate cell growth and division) bind to this receptor, they activate a signaling system inside the cell that ultimately promotes diverse functions such as growth, interaction and adhesion between cells, and the ability of the cell to migrate within tissues. In some tumors, the activation of HER3 signaling is an important mechanism that drives the disease process. This can occur through genetic alterations in the ERBB3 (HER3) gene including amplification, overexpression, or gene mutation in the cancer cells.
The ERBB3 (HER3) gene has been found to be genetically altered (gene amplification, overexpression, or mutation) in a number of different cancers. These include breast, stomach, ovary, prostate, colon, pancreas, oral cavity, and lung. The genetic alterations seen in ERBB3 (HER3) in cancers cause increased amounts of the receptor to be produced, or, in the case of mutations, cause the protein to be activated even in the absence of stimulation by growth factor-binding. The excess or activated ERBB3 (HER3) interacts with other members of the ERBB family of growth factor receptors, sending signals through a series of protein cascades in the cell that cause the cells to grow and divide in an uncontrolled manner. Genomic testing of tumors in labs such as the one at MGH can identify the presence of genetic alterations in ERBB3 (HER3), and help clinicians make appropriate decisions about treatment with therapeutic agents that target the ERBB3 (HER3) receptor itself, or that target the growth signal pathways activated by HER3 (ERBB3) and its’ family member partners. These drugs are currently being studied in clinical trials as treatments for patients with tumors harboring genetic alterations in HER3 (ERBB3). Pertuzumab is a drug that blocks HER2:HER3 dimerization and is FDA approved for treatment of HER2 positive breast cancer.
Scientific studies on tumors from patients has also demonstrated that ERBB3 (HER3) plays an important role in the development of resistance to cancer therapies, particularly anti-HER2 therapies and other targeted therapies modulating the PI3K/AKT/mTOR pathway and MAP kinase/ERK pathways in cancer. Patients who are initially treated and respond to some cancer therapies subsequently develop genetic alterations in ERBB3 (HER3), which play a central role in relapse or resistance to the initial treatment. More clinical studies are needed that identify strategies for preventing the emergence of resistance in patients to ERBB3 (HER3) therapy, and for improved treatment of tumors with identified ERBB3 (HER3) genetic alterations. Clinical trials directly targeting ERBB3 (HER3) are underway, as are therapies targeting downstream pathways that are activated by the receptor.
Source Genetics Home Reference
The ERBB3 (HER3) gene encodes a cell surface protein that belongs to the ERBB family of receptor tyrosine kinases, known as ErbB3 (more commonly referred to as HER3). Four members of the ERBB family have been identified; EGFR (ERBB1, HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). The binding of a ligand induces ERBB receptor homo-/hetero-dimerization, which activates and subsequently triggers a signaling cascade that drives many cellular responses. These include the activation of PI3K/AKT/mTOR and MAP kinase/ERK pathways, which promote cell survival and proliferation. Although there are several known ligands for ERBB3 (HER3) including neuregulin, ERBB3 (HER3) is an obligate heterodimerization partner with other ERBB family members, as the kinase domain is not functional. ERBB2 (HER2) is the preferred dimerization partner for ERBB3 (HER3), and this heterodimer is catalytically more active than any other dimerization pairing within the ERBB family. ERBB3 plays a role in normal embryogenesis, but is found to be genetically altered through amplification, overexpression, or mutation in a wide array of cancers including breast, stomach, ovary, prostate, colon, pancreas, oral cavity, and lung, among others.
Genetic alterations including amplification, overexpression, and mutations in ERBB3 (HER3) have also been identified as an important mechanism driving tumor growth, and also in conferring resistance to targeted therapies. Clinical trials directly targeting ERBB3 (HER3) are underway, as are therapies targeting downstream pathways activated by the receptor.
Source: Genetics Home Reference
The mutation of a gene provides clinicians with a very detailed look at your cancer. Knowing this information could change the course of your care. To learn how you can find out more about genetic testing please visit http://www.massgeneral.org/cancer/news/faq.aspx
or contact the Cancer Center.