PI3K/AKT/mTOR signaling as a molecular target in head and neck cancer.


:The aim of this review is to summarize current available information about the role of PI3K/AKT/mTOR signaling in head and neck cancer as a potential target for new therapy options. 90% of all head and neck cancers are squamous cell carcinomas (HNSCC). The most common genetic alteration is inactivation of p16 gene which is cyclin dependent kinase inhibitor 2A. HNSCC are divided into human papilloma virus (HPV) related and HPV-negative carcinomas. HPV related carcinomas of patients who do not have a history of tobacco and alcohol consumption have better prognosis. Until now, HNSCC are treated with surgical removal of cancer tissue in primary region and lymph nodes combined with radiotherapy, cytostatic drugs and in some cases, epidermal growth factor receptor (EGFR) targeted antibody cetuximab and programmed death receptor-1 (PD-1) antibodies. PI3K/AKT/mTOR signaling is active in over 90% of HNSCC, as a result of EGFR activation (47%), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations (8.6%), PIK3CA amplifications (14.2%), phosphatidylinositol 3-kinase (PI3K) overexpression (27.2%) and phosphatase and tensin homolog (PTEN) mutation (10-15%). Activated PI3K/AKT/mTOR signaling is related to radiotherapy and cytostatic drug resistance, likely through enhanced DNA-repair mechanisms. Inhibitors against PI3K, AKT and mammalian target of rapamycin (mTOR) have remarkable effects on tumor cell proliferation and radiotherapy sensitization in cell cultures and mouse models. Nevertheless, feedback mechanisms, like activation of AKT after mTOR treatment, reduce efficiency. Therefore, combined therapy should be investigated. PI3K, AKT and mTOR inhibitors achieved tumor response in 5.3%, 2.8% and 31% when given as monotherapy, respectively. When combined to cytostatic drugs, 29.2% and 43.5% of all patients showed a response to PI3K and mTOR inhibitors, respectively. A study investigating everolimus (Rad001) with cisplatin and radiotherapy has reported promising 2-year progression free survival and overall survival rates of 85% and 92%. Further clinical trials should follow.


Biochem Pharmacol


Biochemical pharmacology


Marquard FE,Jücker M




Has Abstract


2020-02-01 00:00:00












  • Apoptosis or necrosis: intracellular levels of glutathione influence mode of cell death.

    abstract::The effect of lowering intracellular glutathione (GSH) concentrations on the toxicity of alkylating agents, and RNA synthesis inhibitor and topoisomerase 1 and 2 inhibitors to a number of human leukaemic cell lines were evaluated. By using the GSH synthesis inhibitor DL-buthionine-(S,R)-sulfoximine (BSO), GSH levels w...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Fernandes RS,Cotter TG

    更新日期:1994-08-17 00:00:00

  • Inhibition of cytochrome P-450p (P450IIIA1) gene expression during liver regeneration from two-thirds hepatectomy in the rat.

    abstract::Regenerating liver from partial hepatectomy (HPX) is known to exhibit a strong and transient deficiency in both spectrally detectable microsomal cytochrome P-450 (P-450) and related monooxygenase activities. Male Wistar rats (250-300 g) were HPX or sham operated and liver was excised at different times after operation...

    journal_title:Biochemical pharmacology

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    abstract::Neurotoxic esterase (NTE) is a membrane-bound protein found in highest concentration in brain and lymphocytes. The enzyme has no known physiological function, but its organophosphorylation and aging in neural tissue are thought to trigger the pathogenesis of organophosphorus-induced delayed neuropathy (OPIDN). Solubil...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Davis CS,Richardson RJ

    更新日期:1987-05-01 00:00:00

  • Affinity, potency, efficacy, selectivity, and molecular modeling of substituted fentanyls at opioid receptors.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


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    更新日期:1990-03-15 00:00:00

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    更新日期:1984-07-01 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    更新日期:1992-04-01 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    更新日期:1994-10-18 00:00:00

  • Suramin modulates cellular levels of hepatocyte growth factor receptor by inducing shedding of a soluble form.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    abstract:OBJECTIVE:The evolution of the "cholinergic anti-inflammatory pathway" and the fact that the α 7 subunit of the nicotinic acetylcholine receptor (α7nAChR) is present in the spleen, joint and on the surface of lymphocytes, opened up the prospective in this study of targeting the α7nAChR by the anticholinesterase and cho...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Gowayed MA,Rothe K,Rossol M,Attia AS,Wagner U,Baerwald C,El-Abhar HS,Refaat R

    更新日期:2019-12-01 00:00:00

  • [3H]N-Methylscopolamine binding to muscarinic receptors in intact adult rat brain cell aggregates.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    更新日期:1985-12-15 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Yoshida T,Mio M,Tasaka K

    更新日期:1992-10-06 00:00:00

  • DNA methyltransferase inhibitors in cancer: From pharmacology to translational studies.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Pechalrieu D,Etievant C,Arimondo PB

    更新日期:2017-04-01 00:00:00

  • Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF).

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


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    更新日期:2016-11-01 00:00:00

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    abstract::Gabexate mesylate is a non-antigenic synthetic inhibitor of trypsin-like serine proteinases that is therapeutically used in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. Considering the structural similarity between gabexate mesylate and argi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Erba F,Fiorucci L,Pascarella S,Menegatti E,Ascenzi P,Ascoli F

    更新日期:2001-02-01 00:00:00

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    abstract::The effects of p-chloromercuribenzoate and N-ethylmaleimide were evaluated on the binding of (3H)-p-aminoclonidine, (3H)-rauwolscine and (3H)-prazosin on rat brain alpha-adrenergic receptors. Pretreatment of the particulate fraction with increasing concentrations of p-chloromercuribenzoate indicated that the binding o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Quennedey MC,Bockaert J,Rouot B

    更新日期:1984-12-15 00:00:00

  • The protein Nod2: an innate receptor more complex than previously assumed.

    abstract::For almost 10 years, Nod2 has been known as a cytosolic innate receptor able to sense peptidoglycan from Gram-positive and -negative bacteria and to trigger RIP2- and NF-κB-mediated pro-inflammatory and antibacterial response. Mutations in the gene encoding Nod2 in humans have been associated with Crohn's disease (CD)...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


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    更新日期:2010-12-15 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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  • Effect of anthracyclines on phospholipase A2 activity and prostaglandin E2 production in rat gastric mucosa.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    更新日期:1993-08-03 00:00:00

  • Sulphate conjugation of minoxidil in rat skin.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wong KO,Tan AY,Lim BG,Wong KP

    更新日期:1993-03-09 00:00:00

  • Actin cytoskeleton, tubular sodium and the renal synthesis of dopamine.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Soares-da-Silva P

    更新日期:1992-11-03 00:00:00