by reducing smooth muscle cell hyperplasia in the inner layer of the vessels25

by reducing smooth muscle cell hyperplasia in the inner layer of the vessels25. 2. not conducted. The search yielded 97 results. Only articles related to EGFR and VEGFR inhibition were selected. Finally 13 articles met the criteria. Results are discussed and possible pathogenetic mechanisms for the complications of targeted cancer therapy regimens are presented. Results: It appears that the most serious side-effect is mucositis/stomatitis S1PR1 that may affect the whole gastrointestinal tract. It rarely results in treatment discontinuation. Reduced saliva secretion, xerostomia and dysphagia can be severe with some regimens and interfere with food uptake. Osteonecrosis, wound healing impairment, spontaneous gingival bleeding and dysgeusia were also reported. Conclusions: Considering these data it is obvious that symptoms related to cancer treatment should be considered in the context of the holistic management of patients. Oral Pyrintegrin complications should not be ignored but recorded during physical examination, because they may significantly impair daily activities and patients’ quality of life. strong class=”kwd-title” Keywords: bevacizumab, cetuximab, oral complications, molecularly targeted drugs, EGFR, VEGFR Introduction The first to describe a concept of selective uptake of molecules by tissues was Ehrlich, in the 19th century. He described the side-chain theory, that formed the basis for the understanding of the effects of serum and the coupling between an antigen and an antibody, that built the basis for the discovery of monoclonal antibodies and targeted cancer therapy. Molecularly targeted drugs interact with a specific Pyrintegrin target, mostly a protein, in a selective way. This protein is a growth factor, a growth factor receptor, a signaling molecule, a cell cycle protein, an apoptosis mediator, a molecule implicated in cancer cell dispersal and angiogenesis1. Side effects of molecularly targeted drugs differ on the severity of reported symptoms compared to classical chemotherapy agents, because they rarely cause alopecia, nausea and vomiting. Reports regarding oral complications are sparse and the most frequently reported sign in clinical control trials is mucositis/stomatitis. The aim of this review of the literature is twofold: 1. to present the oral complications of targeted cancer therapy, in particular those that are the result of therapies that target EGFR and VEGFR, 2. to analyze the possible pathogenetical mechanisms. Molecularly targeted drugs This general term includes two main categories of molecules, monoclonal antibodies and tyrosine kinase inhibitors. Tyrosine kinase inhibitors connect to the cytoplasmic side of membrane receptors. They are small molecules, administered per os, once daily. Because of their small size they provide enhanced bioavailability. On the contrary, monoclonal antibodies act on the extracellular domain side. They are large molecules, given by intravenous route once a week and show decreased bioavailability in certain compartments, like the CNS. Because of their size they do not normally pass the basal membrane, thus they are rarely related to symptoms from the gastrointestinal tract. They connect to a certain epitope of an antigen/protein. Receptors: action and side-effects 1. EGFR EGF receptors are membrane receptors with tyrosine kinase activity. Like all receptors of this family, they need ATP for the phosphorylation of their cytoplasmic domain, that possesses enzymatic activity. They play a major role in cancer progression, because they inhibit apoptosis, enhance cell cycle progression, angiogenesis, cancer cell motility and metastasis, malignant transformation and lead to cancer phenotype2,3. The overexpression of EGFR in various cancer types, especially in the head and neck cancer, in which an overexpression is present in 42%-98% of the cases, is related to an increased transcriptional activity and anticipates a bad outcome2,3. EGFR inhibition and oral complications Two different ways of EGFR-molecularly targeted drug interaction offer a more effective inhibition. The 1st involves the connection of the drug to the extracellular website of the receptor that inhibits the connection of the ligand. The second Pyrintegrin focuses on the intracellular portion that has tyrosine kinase activity and exerts its action by restricting ATP binding or binding to the active site of the enzyme3,4. Therefore both monoclonal antibodies and tyrosine kinase inhibitors can efficiently inactivate EGFR. EGFR inhibition is related to malignancy cell apoptosis and cell cycle arrest via p27 activation, a cyclin dependent inhibitor, as well as with anti-angiogenic effects. The last is an interesting aspect of EGFR inhibition and may become explained through the connection of this receptor with the VEGF, the main factor in angiogenesis. In particular, inhibition of EGFR is related to decreased manifestation of VEGF and decreased VEGF manifestation correlates with decreased EGFR levels5,6. Nonetheless, an anti-EGFR medication cannot completely get rid of VEGF plasma levels. Additionally, EGFRs are present within the endothelium of malignancy vascular cells and are related to the vascular denseness of mammary carcinomas7,8. Mucositis It is interesting that most of the phase I-III clinical tests, do not thoroughly statement oral complications for cetuximab, a monoclonal antibody that functions as an EGFR inhibitor9. Stomatitis is definitely a frequent (Table 1)10-19, dose self-employed, sign and it is characterized by generalized erythema and level of sensitivity and hardly ever by ulcerous lesions as in case of.