Targeted therapy in head and neck cancer

ENT Department, University Hospital of Ferrara, Ferrara, Italy.
Tumori (Impact Factor: 1.27). 03/2011; 97(2):137-41. DOI: 10.1700/667.7773
Source: PubMed


This review focuses on recent advances in understanding the molecular mechanisms at the basis of cancer initiation and progression in the head and neck and also discusses the possible development of targeted cellular strategies. Intrinsic and acquired resistance of cancer cells to current conventional treatments, as well as recurrence, represent a major challenge in treating and curing the most aggressive and metastatic tumors also in the head and neck. Even though in some hematologic malignancies (i.e., non-Hodgkin's lymphomas) antibodies specifically designed to target tumor-specific cells have already been introduced, in solid tumors molecular targeted therapy is now entering clinical practice.
A PubMed database systematic review.
Molecular targeting could achieve specific damage to cancer cells, at the same time preserving functionally important tissues. This could offer new prospectives in primary and adjuvant treatment also of head and neck tumors.

Download full-text


Available from: Stefano Pelucchi,
  • Source
    • "Principle The concept of 'Field cancerization', coined by Slaughter in 1953, proposes that the normal tissue adjacent to the tumor harbor certain pre-neoplastic genetic finger prints which can eventually lead to development of local recurrence or second primary tumors. Slaughter and his group based this concept on the following observations: (i) tumor adjacent mucosa being molecularly 'abnormal' (ii) multifocal areas of precancerous changes develop due to a prolonged and widespread exposure to carcinogens (iii) oral cancer often consists of multiple independent lesions that sometimes coalesce and (iv) formation of second primary tumors and recurrences can be explained by the presence of residual abnormal tissue after surgery [15] [16]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Oral squamous cell carcinoma (OSCC) has a high propensity for local failure, which is attributed to recurrence at the primary site or the development of second primary tumors (SPT). Field cancerization that refers to the existence of transformed cells in areas adjacent to the primary tumor, has been attributed to be one of the probable reasons underlying disease relapse. The carcinogenic process necessitates multiple molecular events for the transformation of a normal cell into a cancer cell. This implies that only the long-time residents of the epithelium, such as the stem cells, might be the candidates capable of accumulating these genetic hits. These transformed stem cells- the 'Cancer stem cells' (CSCs), are further known to be equipped with the properties of tumor initiation and migration, both of which are essential for orchestrating field cancerization. The concept that the CSCs might be responsible for field cancerization in OSCC has not been explored extensively. If the role of CSCs as the primary units of field cancerization process is established, their presence in the mucosa adjacent to the tumor may be an indicator for local recurrence and/or development of second primary tumors. In this review, we examine the available evidence in literature exploring the possibilities of CSCs driving the process of field cancerization and thereby being the underlying mechanism for disease recurrence and development of SPT. Published by Elsevier Ltd.
    04/2015; 51(7). DOI:10.1016/j.oraloncology.2015.04.006
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To investigate the efficacy of the bispecific targeted toxin, dEGFATFKDEL, on head and neck carcinoma cell lines in vitro and in vivo. Materials and methods: A deimmunized bispecific anti-cancer agent was constructed to simultaneously target both the overexpressed EGF receptor on carcinomas and the urokinase receptor (uPAR), that is found on the endothelial cells of the neovasculature within tumors. Flow cytometry assays were performed to determine the level of EGFR expressed on a variety of carcinoma lines. These lines were then tested in tritiated leucine incorporation assays to determine the efficacy of dEGFATFKDEL. Human vein endothelial primary cells were also tested to determine the effectiveness of the ATF portion of the molecule that binds uPAR. Furthermore, mouse studies were performed to determine whether dEGFATFKDEL was effective at inhibiting tumor growth in vivo. Results: UMSCC-11B and NA, two head and neck squamous cell carcinomas, highly expressed EGFR. Both the carcinoma lines and the human vein endothelial cells were inhibited at sub-nanomolar concentrations by dEGFATFKDEL. The tumor studies showed that the tumors treated with dEGFATFKDEL were significantly inhibited whereas the negative control and untreated tumors progressed. In a separate in vivo study involving another carcinoma line, MDA-MB-231, the effectiveness of dEGFATFKDEL was confirmed. No toxicity was seen at the doses used in either of these mouse studies. Conclusions: This bispecific agent is effective in a mouse model of head and neck squamous cell carcinoma. Further study of this reagent for use in the treatment of carcinomas is warranted.
    Oral Oncology 07/2012; 48(12). DOI:10.1016/j.oraloncology.2012.06.002 · 3.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Increasing information concerning molecular biology of viruses and virus-cell interactions makes possible to use viruses as a tool in effort to treat cancer diseases. As a rule, tumor cells are highly sensitive to viruses that may be used in cancer therapy. Therewith, applications of viral oncolysis in treatment of cancer diseases assume maximum possible safety of used viruses for patient and environment. Human enteroviruses are one of the convenient sources to generate oncolytic viruses. Many of enteroviruses are non-pathogenic for humans or cause mild disease. Progress in genetic engineering permits to develop attenuated enterovirus variants with high safety and selectivity. This review focuses on the main members of Enterovirus genus, such as Coxsackieviruses, and vaccine strains as promising source for development of oncolytic agents, applicable for cancer therapy. It reviews data concerning recently developed and tested oncolytic variants of enteroviruses and discusses perspectives of their application in cancer therapy and problems, concerning their improvement and practical use.
    Molecular Biology 09/2012; 46(5-6):712-725. DOI:10.1134/S0026893312050032 · 0.72 Impact Factor
Show more