HER2 GENE:

DEFINITION AND
SIGNIFICANCE
 OUTLINE

01 02 03
Introduction to HER2 Overview of HER2 HER2 Gene
Gene Gene Structure and Overexpression
Function

04 05 06
HER2 Testing and
HER2 Related Treatment Options
Conclusion
Cancers for HER2-Positive
Cancers
INTODUCTION TO HER2 GENE
The human epidermal growth factor receptor 2
(HER2) is 1 of the 4 membrane receptor tyrosine
kinases (RTKs).

HER2 oncogene is a member of the human epidermal growth

factor receptor family located on chromosome 17q12.

The sequence of the neu oncogene was homologous to the erb-B

oncogene and its 185 kD phosphoprotein was antigenetically
related to the epidermal growth factor receptor.

The other members in the epidermal growth factor

receptor family are; HER1 (EGFR), HER3 (erbB3), and
HER4 (erbB4).
HER2 STRUCTURE AND FUNCTION
HER2 is a transmembrane protein with a molecular
weight of 185 kDa.

It can form heterodimers with other HER family

members

The ERBB2 (HER2) protein is composed of a

polypeptide chain consisting of a total of 1255 amino
acids.

These amino acids serve as the basic building blocks

of the protein and come together to form the
polypeptide chain.
 HER2 GENE
OVEREXPRESSION
HER2 activates proliferative and anti-apoptosis signals, driving
tumor development and progression. Identifying HER2
overexpression or amplification makes it a valuable treatment
target.

Overexpression and amplification can cause

homodimerization of HER2 proteins on the
membrane.

Dimerization of the receptor results in the

autophosphorylation of tyrosine residues within
the cytoplasmic domain of the receptors and
initiates a variety of signaling pathways leading
to cell proliferation and tumorigenesis.
 HER2 OVEREXPRESSION-
RELATED CANCERS
Normal tissues have a low complement of HER2 membrane protein. Overexpression of
HER2 is seen in 20% of breast and in some ovarian and gastric cancers, and it confers
worse biological behavior and clinical aggressiveness in breast cancer

Amplification or overexpression of HER2:

Occurs in approximately 15–30% of breast cancers.
Occurs in 10–30% of gastric/gastroesophageal cancers.
Serves as a prognostic and predictive biomarker.
HER2 overexpression has also been observed in other cancers:
Ovary
Endometrium
Bladder
Lung
Colon
Head and neck
 HER2 TESTING AND TREATMENT
OPTIONS FOR HER2-POSITIVE
CANCERS
Currently HER2 testing is carried out by several methods: immunohistochemistry (IHC),
fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH) and silver
enhanced in situ hybridization (SISH)

Immunohistochemistry (IHC) detects HER2 protein overexpression using monoclonal or

polyclonal antibodies that bind to the protein.

HER2 testing results by IHC fall into three categories, positive, equivocal and negative.
Each of these results triggers different patient management
Score 0 HER2/neu Score +1 HER2/neu
stainig in breast stainig in breast
cancer cancer

Score +2 HER2/neu Score +3 HER2/neu

stainig in breast stainig in breast
cancer cancer
 EFFECTIVE DRUGS
There are two FDA-approved drugs for cancers caused by HER2 overexpression. The
first drug is trastuzumab, which recognizes the HER2 external domain and primarily
targets HER2 proteins that undergo homodimerization.

Approximately 25% of cancer patients with HER2 overexpression have shown positive
responses to trastuzumab treatment.

Another FDA-approved drug besides trastuzumab is doxorubicin. As known, the HER2

gene located on chromosome 17 is accompanied by the topoisomerase 2 alpha gene,
which is also positioned on chromosome 17.
 CONCLUSİONS

01 The HER2 oncogene is an important member of the HER family

of membrane tyrosine kinases.

02
The gene is amplified in a subset of breast cancers in which the
HER network is the major driver of tumor cell proliferation and
survival.

03
Targeting this pathway therapeutically has remarkably
improved the outlook of patients with these aggressive breast
cancers, but treatment is only effective in patients whose tumors
express high levels of the protein or are amplified for the gene.
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