title: Targeting the PI3K Pathway in Head and Neck Squamous Cell Carcinoma.
abstract: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosal epithelia in the head and neck region. The most common risk factors are tobacco use, alcohol consumption, and HPV infection, particularly in the oropharynx. The HPV-positive HNSCC is biologically and clinically distinct from the HPV-negative HNSCC; however, deregulations within the phosphatidylinositol 3-kinase (PI3K) pathway are frequent in both HPV-positive and HPV-negative HNSCC as it is the most frequently altered oncogenic pathway with a gain-of-function in HNSCC. This article reviews the basic biology and clinical data from the trials involving anticancer agents targeting the PI3K pathway in HNSCC. It also discusses the difficulties of translating the preclinical data to tangible clinical efficacy of these agents in patients with HNSCC even when there is significant preclinical data suggesting the PI3K pathway is a promising therapeutic target in HNSCC. We conclude that additional studies to determine appropriate patient selection for the activation of PI3K pathway and to develop targeted agents either as a monotherapy or combination therapy with favorable toxicity profiles are required before a broader clinical application.
authors.affiliation: From the Department of Clinical Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; Department of Oncology and Department of Head and Neck Surgery-Otolaryngology, The Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Pedro Henrique
authors.initials: PH
authors.lastname: Isaacsson Velho
authors.affiliation: From the Department of Clinical Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; Department of Oncology and Department of Head and Neck Surgery-Otolaryngology, The Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Castro
authors.affiliation: From the Department of Clinical Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; Department of Oncology and Department of Head and Neck Surgery-Otolaryngology, The Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism*; D055808:Drug Discovery; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000077195:Squamous Cell Carcinoma of Head and Neck; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases