Unveiling the Mystery of erb - B2/CD340/HER2

In the field of cancer research, erb - B2 (also known as c - neu, HER2 or CD340) is like a highly - prominent "star molecule", playing an extremely crucial role in the occurrence and development of tumors. The proto - oncogene ErbB2 encodes a receptor tyrosine kinase, which is frequently over - expressed in numerous human tumors.

Structure and Function

HER2 has a unique structure, consisting of three important parts: the extracellular ligand - binding domain, the transmembrane domain, and the intracellular domain. This elaborate structure endows HER2 with powerful functions. It can interact with a large number of signaling molecules, demonstrating both ligand - dependent and ligand - independent activities. Precisely because of these characteristics, HER2 plays a key role in the life activities of cells. By binding to various growth factors, it induces important processes such as cell proliferation, differentiation, and survival. However, when this balance is disrupted and ErbB2 experiences abnormalities such as mutations, over - expression, and gene amplification, it is like opening a "Pandora's box". Tumor cells then start to grow and infiltrate unrestrainedly, thereby participating in the occurrence and development processes of multiple cancers. Breast cancer, gastric cancer, and ovarian cancer are typical examples.

In tumor cells with high erb - B2 expression, the internal environment of the cells seems to be in a state of "crazy growth". At this time, the activities of Ras - MAPK and PI3K - Akt signaling pathways are significantly increased, and the cell proliferation ability becomes extremely strong. At the same time, the cell differentiation, maturation, and apoptosis mechanisms are severely inhibited, and the malignancy of the cells rises sharply. What's more troublesome is that such tumor cells seem to be clad in an "immune armor", being able to resist the apoptosis effects induced by TNF - α, radiation, and various chemotherapeutic drugs. Clinically, the expression level of erb - B2 is closely related to the prognosis of patients. Patients with high erb - B2 expression are, as if "cursed", extremely prone to tumor metastasis, and their survival period is significantly shortened. Fortunately, there is a significant difference in the expression levels of erb - B2 between normal cells and tumor cells. This characteristic makes it an ideal target for tumor immunobiological therapy and also a hot molecule in the current field of tumor treatment research. In recent years, a molecule named Herstatin has come into the spotlight. It is the only naturally occurring self - inhibitory molecule of erb - B2, a product of alternative splicing during the processing of erb - B2 mRNA. As a soluble erb - B2 receptor, it has brought new hope for tumor treatment.

Signal Transduction

As a common receptor for other members of the receptor tyrosine kinase ErbB family, ErbB2 plays a central role in the signal transduction process. Signals are transmitted through ErbB2/ErbB4, ErbB2/ErbB3, and ErbB2/EGF receptor heterodimers. For example, ErbB2/4 and ErbB2/ErbB3 heterodimers transmit neuregulin - 1 signals in the developing heart, adult heart, and peripheral nervous system, respectively. The latest medical research has found that tissue - specific mutations of ErbB2 in cardiomyocytes have revealed its important functions in normal cardiac physiology and also demonstrated that the loss of cardiac ErbB2 can lead to dilated cardiomyopathy in adult mice. This indicates that ErbB2 is not only crucial during development but also essential for the normal function of differentiated myocardium. However, this also presents a dilemma. ErbB2 - targeted tumor suppression therapy may lead to ventricular dysfunction, while activating ErbB2 for the treatment of heart failure may induce malignant tumors.

Clinical Treatment

Significant progress has been made in ErbB2 - targeted therapy. Mutations in the HER2 gene can lead to the abnormal activation of the protein encoded by this gene, thereby promoting the proliferation, metastasis, and invasion of tumor cells and increasing the resistance of tumors to traditional chemotherapeutic drugs. Therefore, the detection and treatment of HER2 have become a key direction in the treatment of multiple tumors. Currently, some drugs for ErbB2 - targeted therapy have been successfully developed. For example, in the treatment of breast cancer, trastuzumab (Herceptin) has become an important target for the biological treatment of nearly 30% of patients with breast malignancies, bringing hope of survival to numerous patients. In the treatment of triple - negative breast cancer, drugs such as toripalimab and lapatinib have also shown good therapeutic effects.

Summary

With the continuous deepening of research, our understanding of the relationship between erb - B2 (HER2) and tumors has become increasingly clear. Although certain achievements have been made in the tumor treatment targeting erb - B2, many challenges still remain. In the future, it is necessary to further study the mechanism of action of erb - B2 in depth and develop more precise and effective treatment methods to overcome tumor drug resistance, improve the survival rate and quality of life of patients, and bring more hope to cancer patients.