How is the HER2 pathway activated?

How is the HER2 pathway activated?

Upon phosphorylation of its tyrosine kinase domain, HER2 promotes proliferation by activation of the RAS-MAPK-pathway and survival through PI3K-AKT-pathway [31].

What type of receptor is HER2 and why is it important?

HER2 belongs to the human epidermal growth factor receptor family, which includes EGFR (alias HER1), HER3, and HER4. HER2 works as an oncogene in several cancers including breast cancers, manifesting its effect of carcinogenesis mainly by overexpression or due to gene amplification.

What is the normal function of HER2?

The HER2 gene makes HER2 proteins (also sometimes referred to as HER2/neu proteins). HER2 proteins are receptors on breast cells. Normally, HER2 receptors help control how a healthy breast cell grows, divides, and repairs itself.

What causes HER2 gene amplification?

This is caused by a mutation in the HER2 (human epidermal growth factor receptor 2) gene. When the HER2 gene mutates, it causes cells in the breast to grow and divide at an uncontrolled rate, leading to tumor growth.

What binds to HER2 receptor?

Known as a HER dimerization inhibitor, pertuzumab binds to HER2 ECD and sterically blocks its dimerization with other HER receptors.

What causes HER2 amplification?

In about 25 percent of breast cancers, the cancer cells have an excess of the HER2 protein. This is caused by a mutation in the HER2 (human epidermal growth factor receptor 2) gene. When the HER2 gene mutates, it causes cells in the breast to grow and divide at an uncontrolled rate, leading to tumor growth.

Is HER2 a tumor suppressor gene?

In vivo studies show that these HER2/neu repressors can act therapeutically as tumor suppressor genes for tumors that overexpress HER2/neu. These preclinical studies clearly indicate that transcriptional repressors that downregulate HER2/neu can be effective regimens for cancer treatment in a gene therapy format.

What is the difference between HER2 positive and HER2-negative?

Breast cancer cells with higher than normal levels of HER2 are called HER2-positive. These cancers tend to grow and spread faster than breast cancers that are HER2-negative, but are much more likely to respond to treatment with drugs that target the HER2 protein.

Is HER2-positive or negative Better?

What does HER2 amplification mean?

HER2 (ERBB2: c-erb-b2) is an oncogene on the long arm of chromosome 17 that is amplified in approximately 15% to 20% of breast cancers. Amplification or overexpression of HER2 has been shown to be associated with shorter disease-free survival and poorer overall survival in breast cancers.

What causes overexpression of HER2?

Overexpression of HER2 with IHC without gene amplification may be due to high polysomy of chromosome 17 or may occur through various molecular epigenetic or posttranscriptional events (e.g., DNA hypomethylation in the promoter regions, posttranscriptional events) [18].

What percentage of breast cancers are HER2-positive?

About 15% to 20% of breast tumors have higher levels of a protein known as HER2. These cancers are called HER2-positive breast cancers.

What cancers are HER2-positive?

Cancers that may be HER2 positive include breast, bladder, pancreatic, ovarian, and stomach cancers. Also called c-erbB-2 positive and human epidermal growth factor receptor 2 positive.

What is HER2 overexpression?

Amplification or overexpression of HER2 occurs in approximately 15–30% of breast cancers and 10–30% of gastric/gastroesophageal cancers and serves as a prognostic and predictive biomarker. HER2 overexpression has also been seen in other cancers like ovary, endometrium, bladder, lung, colon, and head and neck.

What is worse triple negative or HER2-positive?

Conclusions: The triple negative subtype has the worst survival regardless of stage. HER2-positive cancers are heterogeneous and not all have poor survival. ER and PR must be considered. ER status appears to influence 5-year survival more than HER2 status.