Abstract:
: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.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Marquard FE,Jücker Mdoi
10.1016/j.bcp.2019.113729subject
Has Abstractpub_date
2020-02-01 00:00:00pages
113729eissn
0006-2952issn
1873-2968pii
S0006-2952(19)30428-9journal_volume
172pub_type
杂志文章,评审abstract::Human immunodeficiency virus type 1 (HIV-1) gene expression is modulated by some virus-encoded proteins, possibly acting at multiple levels of control, which are also known to be involved in the regulation of gene expression in uninfected cells (transcriptional, post-transcriptional, nucleocytoplasmic transport, and t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90078-0
更新日期:1988-10-15 00:00:00
abstract::Indole alkaloids possess a large spectrum of biological activities including anti-protozoal action. Here we report for the first time that voacamine, isolated from the plant Tabernaemontana coronaria, is an antiprotozoal agent effective against a large array of trypanosomatid parasites including Indian strain of Leish...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2017.05.002
更新日期:2017-08-15 00:00:00
abstract::Theophylline, caffeine, isobutylmethylxanthine, papaverine, N6-cyclohexyladenosine, N6-allyl-N6-cyclohexyladenosine ( ACHA ) and N6-L-phenylisopropyladenosine (L-PIA) inhibited the transport of adenosine, uridine and hypoxanthine in Novikoff rat hepatoma cells. The IC50 values for the inhibition of uridine transport r...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90350-2
更新日期:1984-06-01 00:00:00
abstract::The aim of this work is the in vitro and ex vivo assessment of the leishmanicidal activity of camptothecin and three analogues used in cancer therapy: topotecan (Hycantim®), gimatecan (ST1481) and the pro-drug irinotecan (Camptosar®) as well as its active metabolite SN-38 against Leishmania infantum. The activity of c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.02.024
更新日期:2013-05-15 00:00:00
abstract::Hepcidin is a peptide hormone that controls systemic iron availability and is upregulated by iron and inflammation. Heparins have been shown to be efficient hepcidin inhibitors both in vitro and in vivo, even when their anticoagulant activity has been abolished by chemical reactions of oxidation/reduction (glycol-spli...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.09.007
更新日期:2014-12-01 00:00:00
abstract::Eighteen linear analogues of [Arg8]vasopressin (AVP) were synthesized by systematically substituting the cysteine residues at positions 1 and 6 with a range of L-amino acids. Screening by competition ligand binding revealed that the combinations of amino acid residues tolerated at these positions was very restricted w...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90523-1
更新日期:1994-04-29 00:00:00
abstract::Epidemiological and experimental animal data indicate that exposure to both metals and metalloid species exacerbates the risk of human diseases, particularly cancers. Vascular endothelial growth factor (VEGF), which performs a primary function in both tumor progression and angiogenesis, is up-regulated due to exposure...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.03.021
更新日期:2006-06-28 00:00:00
abstract::Aldehyde dehydrogenase (ALDH) is well known for its involvement in the resistance of tumor cells to cyclophosphamide (CPA) and its activated derivatives, such as 4-hydroperoxy-CPA (4HC). The role of other drug-metabolizing enzymes such as glutathione S-transferase (GST) in CPA resistance is, however, less certain. In ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00079-f
更新日期:1995-05-26 00:00:00
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
doi:10.1016/j.bcp.2010.07.016
更新日期:2010-12-15 00:00:00
abstract::Multiple sclerosis (MS) is a severe chronic T cell-mediated autoimmune inflammatory disease of the central nervous system (CNS), the existing therapy of which is only partially effective and is associated with undesirable side effects. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological prop...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2011.11.026
更新日期:2012-02-15 00:00:00
abstract::We have previously shown that chronic administration of the 5-hydroxytryptamine (5-HT) receptor antagonist, ritanserin (10 mg/kg/day) or the monoamine oxidase type A inhibitor (MAOI), clorgyline (2 mg/kg/day), results in a reduction in 5-HT2 receptor number in rat cerebral cortex. This study investigates the effects o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90242-d
更新日期:1990-11-01 00:00:00
abstract::Glucuronidation of quinols of polycyclic aromatic hydrocarbons (PAHs) represents an important detoxication pathway preventing toxic quinone/quinol redox cycles. Therefore, mono- and diglucuronide formation of benzo(a)pyrene-3,6-quinol was investigated and compared to that of structurally related 3,6-dihydroxychrysene ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00095-h
更新日期:1995-05-26 00:00:00
abstract::Partial hepatectomy (PH) (70% resection) causes within 4 hr an accumulation of ornithine decarboxylase (EC 4.1.1.17, ODC) mRNAs concomitant with an increase in ODC activity, maximum values being observed at 8 and 16 hr, respectively. In the early hours of hepatic regeneration, enhancement of transcriptional-rate of OD...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90462-t
更新日期:1990-10-01 00:00:00
abstract::The family of natural red pigments, called prodigiosins (PGs), characterised by a common pyrrolylpyrromethene skeleton, are produced by various bacteria. Some members have immunosuppressive properties and apoptotic effects in vitro and they have also displayed antitumour activity in vivo. Understanding the mechanism o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(03)00496-9
更新日期:2003-10-15 00:00:00
abstract::"Ecstasy" [(+/-)-3,4-methylenedioxymethamphetamine or MDMA] is a CNS stimulant, whose use is increasing despite evidence of long-term neurotoxicity. In vitro, the majority of MDMA is demethylenated to (+/-)-3,4-dihydroxymethamphetamine (DHMA) by the polymorphic cytochrome P450 2D6 (CYP2D6). We investigated the demethy...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01028-6
更新日期:2002-06-15 00:00:00
abstract::Although there are a number of well-characterised animal models available for testing and comparing the efficacy of iron chelators, most are expensive to operate and are not capable of providing rapid and reproducible results. The method described herein is based on the labelling of rat liver with 59Fe using rat 59Fe-...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00319-0
更新日期:1999-03-01 00:00:00
abstract::Developmental correlation of higher levels of estrogen binding by macromolecules in rat liver supernatant and of increases in plasma renin substrate levels after estrogen administration is reported. Gel filtration columns were used to separate bound from free radioactivity in studying binding of radioactive estradiol...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(77)90467-1
更新日期:1977-05-15 00:00:00
abstract::Anti-idiotypic antibodies which recognize the opiate receptor were generated in guinea pigs following immunization against purified rabbit anti-morphine antibodies. The anti-idiotypic antibodies produced a concentration-dependent inhibition of [3H]naloxone binding to opiate receptors in a membranous mouse brain prepar...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90006-1
更新日期:1985-08-15 00:00:00
abstract::Recent experiments from our laboratory have indicated that the inhibitory effect of 3'-azido-3'-deoxythymidine (AZT) on oxidative phosphorylation may occur directly, in addition to being brought about by its inhibition of mtDNA replication. We report here studies on the effect of AZT on adenylate kinase, an enzyme cru...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90564-9
更新日期:1994-10-07 00:00:00
abstract::The role of CYP2E1 in ketone-stimulated insulin release was investigated using isolated pancreatic islets of Langerhans and two mammalian insulin secreting pancreatic beta-cell lines engineered to stably express human CYP2E1 (designated BRIN BD11h2E1 and INS-1h2E1). Isolated rat pancreatic islets were shown to express...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.10.011
更新日期:2004-03-01 00:00:00
abstract::P-450-male is a male specific form of cytochrome P-450 in rat liver microsomes. Cytochrome P-450 crossreactive with anti-P-450-male antibodies was purified to an electrophoretical homogeneity from liver microsomes of male beagle dogs. The specific content of the purified cytochrome P-450 (P-450-D1) was 16.9 nmol/mg pr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90032-4
更新日期:1989-01-15 00:00:00
abstract::The interactions of the anticonvulsant drug milacemide (2-n-pentylaminoacetamide) with rat liver mitochondrial monoamine oxidases-A and -B have been studied. The compound acts as a substrate for the B-form of the enzyme, with an apparent Km value of 49 +/- 4.7 microM and a Vmax value of 1.1 +/- 0.2 nmol/min/mg. It is ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90123-6
更新日期:1994-02-11 00:00:00
abstract::Glutathione (GSH) contributes to the detoxification of anticancer drugs through the operation of specific glutathione S-transferases (GST) and innate, or acquired, overexpression of this enzyme family has been frequently observed in tumor cell lines. In the GMA32 line of Chinese hamster fibroblasts, we showed that GSH...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)00452-r
更新日期:1995-01-31 00:00:00
abstract::The indole alkaloid gramine is found in several plant families. Its effects on mammalian mitochondria and submitochondrial particles were studied. Low concentrations of gramine slightly stimulated basal electron transport, totally inhibited the Ca2+-induced respiratory control and partially abolished the enhancement o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90596-3
更新日期:1984-10-01 00:00:00
abstract::The influence of delta 9-tetrahydrocannabinol (delta 9-THC) on the cellular levels of histone mRNAs and ribosomal RNAs was examined in several normal and transformed human cell lines--HeLa S3 cells, WI-38 human diploid fibroblasts, SV40-transformed WI-38 cells, and A549 lung carcinoma cells. RNA sequences were quantit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90510-0
更新日期:1984-04-01 00:00:00
abstract::Kaposi's sarcoma (KS), a neoplasm often associated with iatrogenic and acquired immunosuppression, is characterized by prominent angiogenesis. Angiogenic factors released from KS and host cells and HIV viral products-the protein Tat are reported to be involved in angiogenesis. Mounting evidence further suggests that m...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.06.012
更新日期:2007-11-01 00:00:00
abstract::The effect of oxidant stress produced by redox cycling of substituted 1,4-naphthoquinones on the activity of platelet (Na(+)-K+)ATPase and the active transport of serotonin (5-HT) was studied. 2-Methyl-1,4-naphthoquinone (menadione) produced a concentration-dependent (0-100 microM) and time-dependent (2-20 min) stimul...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90203-h
更新日期:1991-03-15 00:00:00
abstract::The present study has examined the effect of colchicine and cytochalasin B, two cytoskeleton disrupter compounds, on the formation of dopamine in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA); the deamination of newly formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90085-w
更新日期:1992-11-03 00:00:00
abstract::The 3'-fluoro-and 3'-azido-substituted derivatives of 2',3'-dideoxythymidine (ddThd), 2',3'-dideoxyuridine (ddUrd), 2',3'-dideoxy-5-ethyluridine (ddEtUrd) and 2',3'-dideoxycytidine (ddCyd) have been synthesized and evaluated for their anti-retrovirus activity [against human immunodeficiency virus (HIV) and murine Molo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90049-4
更新日期:1988-07-15 00:00:00
abstract::Adherence of Plasmodium falciparum-infected erythrocytes (IE) to the venular endothelium in brain and other organs is characteristic of cerebral malaria, an often fatal complication in infected individuals. It has been shown that cytoadherence may be mediated through interaction of IE with glycoproteins on host target...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90124-n
更新日期:1991-06-15 00:00:00