title: Investigational drugs for head and neck cancer.
abstract: BACKGROUND
  In the treatment of advanced/metastatic head and neck cancer (HNC), resistance to chemotherapy and to anti-EGFR agents remains a major issue, and new molecular drugs are eagerly awaited. Over the last decade, knowledge of the genetic landscape of HNC has rapidly grown. However, no tailored therapeutic intervention targeting HNC molecular abnormalities is currently available outside from clinical trials.
  
  
  METHODS
  In this review, the authors analyze new drugs in the HNC setting which have been investigated in recently published trials or are currently being investigated. The article excludes strategies directed towards the EGFR pathway and antivascular agents.
  
  
  CONCLUSIONS
  Agents acting on the PI3K axis have a strong biological rationale and show the preliminary signs of activity, in particular when combined with other agents. There is limited clinical data of the other discussed pathways; the CMET/HGF pathway as a possible modulator of anti-EGFR drug sensitivity and agents directed towards MEK, WEE-1, NOTCH represent new interesting approaches to HNC. It is of the utmost importance to try and incorporate the molecular dissection of the tumor profiles in clinical trials with such agents. Moreover, the mutational status of other cross-talking pathways should be assessed, since potential resistance mechanisms can be recognized and possibly overcome by a careful selection of patients and combination regimens. Immunotherapy represents a growing field in HNC and its wider application will impact on future therapeutic strategies, including the association with chemotherapy, targeted agents and radiation.
authors.affiliation: a Head and Neck Medical Oncology Department , Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bossi
authors.affiliation: a Head and Neck Medical Oncology Department , Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Alfieri
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D058990:Molecular Targeted Therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D019869:Phosphatidylinositol 3-Kinases
keywords: HDAC; HGF/CMET; MEK; NOTCH; PI3K/AKT/mTOR/PTEN pathway; WEE1 inhibitors; head and neck cancer; immunotherapy; proteasome