Manysided herceptin action in HER2 overexpressing cells

The present state of art is presented on various mechanisms of Herceptin action in cancer cells with overexpression of HER2 receptors, that is p185 protein. Basic and clinical studies justified the introduction of monoclonal antibody against p185 protein (Herceptin) to antitumour treatment and made possible to develop a modern strategy of therapeutic management, called receptor enhancement chemosensitivity (REC). It is based on the phenomenon of sensitization by Herceptin of malignant cells with HER2 receptor overexpression to chemical antitumour preparations. In the result of such sensitization, a chemotherapeutic agent administered in combination with the antibody reaches selectively tumour cells with HER2 receptor overexpression. Since it is administered onto molecular target, that is onto a definite oncoprotein which, in this case, is HER2 receptor protein.

Also studies on the receptors of the HER family performed by other authors demonstrated that the development and progression of malignant phenotype of epithelial tumours with p185 receptor overexpression are based on a three-point axis determined by the effects of three oncoproteins mutually regulating each other: heterodimer of HER2 and HER3 receptors, heregulins (HRG) produced by autocrine mechanism and cyclo-oxygenase 2 (COX2). The central link of this axis is HER2/HER3 heterodimer. The blockade of this link by Herceptin neutralizes mitogenic activity of the remaining two oncoproteins. In the case of autocrine heregulins, this heterodimer is the main element in transmisson pathway of mitogenic signals by heregulins while in the case of cyclo-oxygenase 2, this heterodimer induces oncogenic, constitutional COX 2 gene activation.