ERBB4

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ERBB4

A gene on chromosome 2q33.3-q34 that encodes a single-pass type-1 membrane protein member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. ERBB4 binds to and is activated by neuregulins and other factors, and it induces various cellular responses, including mitogenesis and differentiation.

Molecular pathology
ERBB4 mutations have been associated with cancer.
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A parallel nomenclature for ErbB family frequently used in the scientific field is human epidermal growth factor receptors, HER1 to HER4 [24].
Puma Biotechnology's neratinib is an orally-administered TKI that binds irreversibly, targeting HER1, HER2, and HER4. Neratinib inhibits HER2 at a different site than the currently marketed HER2-targeted therapies, which Puma believes will make it effective in patients who have developed resistance to these other treatments.
The family consists of 4 members, also known as the epidermal growth factor receptors (EGFR): ErbB1 (HER1), ErbB2 (HER2 or Neu), ErbB3 (HER3), and ErbB4 (HER4) [1].
Figure 1 [13] shows the main transduction pathways regulated by the four HER family members--EGFR, HER2, HER3, and HER4.
The seven classes are defined by different combinations and levels of 10 proteins found in breast cancer cells, including ER and HER2, but also others not currently tested, such as p53, cytokeratins, HER3 and HER4.
Notch receptors, CD44, Her4, E-cadherin, EpCAM, MUC-1, etc.) [4].
The epidermal growth factor receptor (EGFR) is a member of the family of transmembrane protein kinase receptors known as the erbB or HER receptor family: EGFR (HER1 or erbB1), erbB2 (HER2), erbB3 (HER3) and erb4 (HER4).
Currently, the most actively investigated is the family of EGF receptors, which include HER1, HER2, HER3, and HER4. These receptors are found on many cancer cells, notably breast cancer, and correlate with a poor prognosis (Gale, 2003; Gemmill & Idell, 2003).
Varlitinib is a highly potent pan-HER inhibitor that targets the human epidermal growth factor receptors HER1, HER2 and HER4. At ESMO, new data will be presented from a phase 1 study to determine the safety and maximum tolerated dose (MTD) of varlitinib in combination with modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) up to 9 cycles followed by varlitinib monotherapy in advanced solid tumours.
For example, using Sanger sequencing, Vlenterie et al (3) were able to identify 8 novel somatic mutations in the following genes: KRAS, CCND1, SEPT09, RNF213, KDR (VEGFR2), CSMD3, MLH1, and ERBB4 (HER4).
The family of ErbB consists of four members, such as epidermal growth factor receptor (EGFR) and the EGFR-related receptors: HER2, HER3, and HER4 [51].