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What is the role of her2 as a therapeutic biomarker?

Cancer research

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HER2 serves as a crucial therapeutic biomarker in various cancers, including breast, gastric, and colorectal cancers. Its amplification, overexpression, or mutation plays a significant role in tumorigenesis. In colorectal cancer, HER2 amplification occurs in 1-4% of cases, leading to the efficacy of HER2-targeted therapies like pertuzumab plus trastuzumab. Assessing HER2 heterogeneity aids in predicting responsiveness to HER2-directed therapy, emphasizing the importance of accurate HER2 status evaluation. Studies show that HER2 positivity is associated with worse prognosis in colorectal cancer and predicts unresponsiveness to anti-EGFR therapy. Recent trials, like DESTINY-Breast04, highlight the significance of HER2 as a therapeutic target, even in HER2-low metastatic breast cancer, showcasing the evolving landscape of HER2-targeted therapies and the potential of HER2 PET imaging for treatment decisions.

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Open access•Journal Article•DOI A Comprehensive Review on the Role of Human Epidermal Growth Factor Receptor 2 (HER2) as a Biomarker in Extra-Mammary and Extra-Gastric Cancers Fnu Amisha, Paras Malik, Prachi Saluja, Nitesh Gautam, Tanvi H Patel, Arya Mariam Roy, Sunny Singh, Sindhu Janarthanam Malapati - Show less +7 more 26 May 2023-Onco	HER2 serves as a predictive, prognostic, and therapeutic biomarker in breast and gastric cancers, with potential relevance in various other malignancies beyond mammary and gastric origins.
Open access•Journal Article•DOI Molecular Basis of HER2-Targeted Therapy for HER2-Positive Colorectal Cancer Uwe Schirmer 28 Dec 2022-Cancers 4 Citations	HER2 serves as a therapeutic biomarker in colorectal cancer, guiding targeted therapies like dual HER2 antibodies pertuzumab plus trastuzumab for HER2-positive metastatic colorectal cancer.
Patent Her2 heterogeneity as a biomarker in cancer Murillo Adrian E, Nitta Hiro, Munroe Donald G, Lo Amy A, Takeshi Kuwata, Akio Kaito, Atsushi Ochiai - Show less +6 more 11 Mar 2021	HER2 heterogeneity can predict responsiveness to HER2-directed therapy by assessing protein, gene amplification, and RNA status, making it a valuable therapeutic biomarker in cancer treatment.
Journal Article•DOI HER2 positivity as a biomarker for poor prognosis and unresponsiveness to anti-EGFR therapy in colorectal cancer. Wenbai Huang, Yijiao Chen, Wenju Chang, Li Ren, Wentao Tang, Peng Zheng, Qi Wu, Tianyu Liu, Yu Liu, Ye Wei, Jianmin Xu - Show less +10 more 22 Jun 2021-Journal of Cancer Research and Clinical Oncology 4 Citations	HER2 positivity in colorectal cancer indicates poor prognosis and resistance to anti-EGFR therapy, particularly in stage III and IV CRC, serving as a predictive biomarker for therapy unresponsiveness.

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What is Her2?4 answersHER2 is a transmembrane growth factor receptor found in normal and malignant breast epithelial cells. It is a member of the HER family of receptor tyrosine kinases and is encoded by the HER-2 oncogene. Overexpression of HER2 is associated with poor prognosis and resistance to chemotherapy and radiotherapy. HER2 is a valuable treatment target in breast cancer, and its overexpression has independent prognostic significance in early breast cancer. It may also predict response to hormonal and cytotoxic therapies. Anti-HER2 therapy, using a humanized monoclonal antibody, has shown enhanced survival when given with chemotherapy in patients with metastatic HER2-overexpressing breast cancer. HER2 is also being investigated as a promising molecule for immunotherapy strategies.

What is the role of the HER2 gene in normal physiology and in breast cancer?5 answersThe HER2 gene plays a significant role in breast cancer development and progression. HER2 overexpression is observed in a biologically and clinically aggressive subtype of breast cancer. It is responsible for around 25% of breast cancer cases and is involved in the regulation of genes essential for cell growth, apoptosis, and inflammatory signals in breast cancer cells. HER2 gene amplification is a key factor in early malignant transformation and contributes to tumor progression and metastasis. In breast cancer cells, HER2 translocates to the nucleus and binds to enhancer elements, leading to direct gene expression events. Trastuzumab, a targeted therapy, inhibits the growth of HER2-positive breast cancer cells, but some patients eventually develop resistance to it. ECM1 and KRT19 have been identified as proteins involved in trastuzumab resistance and HER2 signaling, respectively. The HER2 gene can be used as a molecular marker for breast cancer.

What is the role of the HER2 gene in normal physiology?5 answersThe HER2 gene is a member of the proto-oncogene family and plays a role in normal cell growth control and differentiation. It is a member of the HER family of receptor tyrosine kinases, which are involved in transmitting signals that control normal cell growth and differentiation. Activation of the HER2 receptor triggers a network of signaling pathways that regulate normal cell growth, motility, and adhesion in various cell lineages. In normal cells, HER2 exists as both monomers and dimers, and ligand binding induces receptor dimerization, with a preference for HER2 as a dimer partner. The HER2 receptor is involved in the regulation of apoptosis and directly regulates programmed cell death. Overall, the HER2 gene has an important role in the network of cell signals controlling normal cell growth and differentiation.

Are there recognized biomarkers for therapeutic alliance?5 answersThere are no recognized biomarkers for therapeutic alliance in the abstracts provided.

What are the potential pitfalls of HER2 targeted therapy?5 answersPotential pitfalls of HER2 targeted therapy include resistance to treatment, cardiotoxicity, and the need for optimization in patient selection and understanding of resistance mechanisms. Resistance to HER2 targeted therapy can occur due to upregulation of dolichyl-phosphate N-acetylglucosaminyltransferase (DPAGT1) leading to sustained HER2 shedding and trastuzumab resistance. Cardiotoxicity is a well-recognized adverse effect of HER2 targeted therapies, and risk factors such as age, low-baseline left ventricular ejection fraction, and treatment with anthracyclines have been identified. Additionally, there is a need for improved patient selection and understanding of resistance mechanisms to optimize the effectiveness of HER2 targeted therapy. These potential pitfalls highlight the importance of ongoing research and the development of strategies to overcome resistance and minimize cardiotoxicity in HER2 targeted therapy.

Breast cancer and HER2?5 answersBreast cancer is a common malignancy among women, and approximately 15-20% of breast cancers are HER2-positive. HER2-targeted therapies, such as trastuzumab and pertuzumab, have significantly improved outcomes for patients with HER2-positive breast cancer. These therapies have increased progression-free survival and overall survival in both early and metastatic disease settings. In addition to monoclonal antibodies, other HER2-targeting agents, including tyrosine kinase inhibitors and antibody-drug conjugates, have shown promise in clinical trials. However, resistance to HER2-targeted therapy remains a challenge, and efforts are underway to develop new strategies and agents to overcome resistance. The accurate quantification of HER2 protein in breast cancer tissue samples using mass spectrometry has the potential to improve treatment customization and patient outcomes. Overall, the development of HER2-targeted therapies has revolutionized the treatment of HER2-positive breast cancer and continues to be an active area of research.

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