Paper jugat pel receptor ErbB-3 (HER-3) en el desenvolupament i tractament del càncer

Abstract

Cancer is one of the most important health problems in the world, affecting a large part of the population. Although there are different treatments such as surgery, radiotherapy or chemotherapy, the cancer currently has no cure, in the strict sense of the word. The numbers of those affected continue to increase, and the future forecasts are not very comforting. Cancer occurs due to alterations in the genes involved in cell growth, survival and propagation, resulting in a set of common characteristics. These characteristics are known as the hallmarks of cancer, and allow to organize and rationalize this complex disease. ErbB (erythroblastic) receptors play a very important role, they’re essential mediators of cell proliferation and differentiation in the development of the embryo and adult tissues, and their inappropriate activation is associated with the development and severity of the cancer. Members of this tyrosine kinase receptor family are: EGFR (ErbB1 or HER1), HER2 (Neu or ErbB2), HER3 (ErbB3) and HER4 (ErbB4). EGFR and HER2 are associated with cancer, since its alteration is found in most cancers. Recently, it has been seen that HER3 receptor also has an important role, in addition, it can act as a new target to treat this disease. Each of these receptors have several ligands with which they bind to be activated, with the exception of HER2 that isn’t known any ligand. Once activated, the receptors dimerize: homodimerization (among them) or heterodimerization (between family members). The heterodimers formed by HER2 and HER3 form the most robust signalling complexes of the ErbB family. One of the characteristics of HER3 is its unique and powerful ability to activate the downstream signalling path PI3K and Akt. It’s key to the control of many biological processes critical for tumorigenesis. In addition, HER3 is also associated with cancer resistance, which is the main problem of current therapies. With these evidences emphasizing the importance of HRE3 signalling in human cancers and their resistance, today there are more than 40 different therapeutic agents that are being tested targeting HER3, in addition to combinatorial therapies that act against different combinations of receptors