Small molecules in combination with conventional chemotherapeutic drugs: Light at the end of the tunnel?

Leinung,Martin; Cuny,Clemens; Diensthuber,Marc; Stöver,Timo; Wagenblast,Jens

doi:10.3892/ol.2012.883

Small molecules in combination with conventional chemotherapeutic drugs: Light at the end of the tunnel?

Authors:
- Martin Leinung
- Clemens Cuny
- Marc Diensthuber
- Timo Stöver
- Jens Wagenblast
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Affiliations: ENT Department, Medical School, Goethe University, Frankfurt am Main, Hessen D-60590, Germany
Published online on: August 28, 2012 https://doi.org/10.3892/ol.2012.883
Pages: 1043-1046

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Abstract

Recent studies have shown BI2536 and bortezomib to be effective in squamous cell carcinoma of the head and neck (SCCHN) cell lines. In this systemic in vitro study, we examined the antitumor effect of the small molecules BI2536 and bortezomib in combination with cisplatin or docetaxel in nine squamous cell carcinoma cell lines, most of head and neck origin. Dose escalation studies were performed with these cell lines using bortezomib, BI2536, cisplatin and docetaxel in cell line-specific concentrations. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and the Human Apoptosis Array kit. The combination of bortezomib and BI2536 with cisplatin or docetaxel showed a significantly higher antiproliferative and apoptotic activity in all SCCHN cell lines investigated compared with single agent cisplatin or docetaxel alone (P≤0.021). Combination of conventional chemotherapeutic drugs, such as cisplatin and docetaxel, with small molecules in the clinical setting may enhance the antitumor activity of these agents and may lead to less toxic side-effects and a more effective cancer therapy.

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1.	H MehannaV PaleriCM WestC NuttingHead and neck cancer - Part 1: Epidemiology, presentation, and preventionBMJ341c4684201010.1136/bmj.c468420855405
2.	G D’SouzaAR KreimerR ViscidiM PawlitaC FakhryWM KochCase-control study of human papillomavirus and oropharyngeal cancerN Engl J Med35619441956200717494927
3.	M PantelO Guntinas-LichiusLaryngeal carcinoma: epidemiology, risk factors and survivalHNO6032402012(In German)
4.	C WittekindtS WagnerJP KlussmannHPV-associated head and neck cancer. The basics of molecular and translational researchHNO598858922011(In German)
5.	JL LefebvreG AndryD ChevalierB LuboinskiL ColletteL Traissacfor the EORTC Head and Neck Cancer GroupLaryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891Ann OncolApr62012(Epub ahead of print)
6.	AA ForastiereT LeongE RowinskyBA MurphyDR VlockRC DeContiGL AdamsPhase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393J Clin Oncol19108810952001
7.	G RameshWB ReevesTNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicityJ Clin Invest110835842200210.1172/JCI20021560612235115
8.	N PablaZ DongCisplatin nephrotoxicity: mechanisms and renoprotective strategiesKidney Int739941007200810.1038/sj.ki.500278618272962
9.	A FribleyQ ZengCY WangProteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cellsMol Cell Biol2496959704200410.1128/MCB.24.22.9695-9704.2004
10.	J WagenblastM HambekM BaghiW GstöttnerK StrebhardtH AckermannR KnechtAntiproliferative activity of bortezomib alone and in combination with cisplatin or docetaxel in head and neck squamous cell carcinoma cell linesJ Cancer Res Clin Oncol134323330200810.1007/s00432-007-0287-917701215
11.	JB SunwooZ ChenG DongN YehC Crowl BancroftE SausvilleNovel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinomaClin Cancer Res714191428200111350913
12.	AM FribleyB EvenchikQ ZengBK ParkJY GuanH ZhangProteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of NoxaJ Biol Chem2813144031447200610.1074/jbc.M60435620016928686
13.	D DattaP BanerjeeM GasserAM Waaga-GasserS PalCXCR3-B can mediate growth-inhibitory signals in human renal cancer cells by down-regulating the expression of heme oxygenase-1J Biol Chem2853684236848201010.1074/jbc.M110.17032420855888
14.	RB RayA RaychoudhuriR SteeleP NerurkarBitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosisCancer Res7019251931201020179194
15.	J WagenblastM BaghiC ArnoldnerS BisdasW GstöttnerH AckermannEffect of bortezomib and cetuximab in EGF-stimulated HNSCCAnticancer Res2822392243200818751401
16.	CW ReuterMA MorganA EckardtTargeting EGF-receptor-signalling in squamous cell carcinomas of the head and neckBr J Cancer96408416200710.1038/sj.bjc.660356617224925
17.	J WagenblastM BaghiC ArnoldnerS BisdasW GstöttnerH AckermannCetuximab enhances the efficacy of bortezomib in squamous cell carcinoma cell linesJ Cancer Res Clin Oncol135387393200910.1007/s00432-008-0477-018830627
18.	A MilanoRV IaffaioliF CaponigroThe proteasome: a worthwhile target for the treatment of solid tumours?Eur J Cancer4311251133200710.1016/j.ejca.2007.01.03817379504
19.	J AdamsThe development of proteasome inhibitors as anti-cancer drugsCancer Cell5417421200410.1016/S1535-6108(04)00120-5
20.	P SchoffskiJY BlayJ De GreveE BrainJP MachielsJC SoriaMulticentric parallel phase II trial of the polo-like kinase 1 inhibitor BI 2536 in patients with advanced head and neck cancer, breast cancer, ovarian cancer, soft tissue sarcoma and melanoma. The first protocol of the European Organization for Research and Treatment of Cancer (EORTC) Network Of Core Institutes (NOCI)Eur J Cancer46220622152010
21.	TL SchmitN AhmadRegulation of mitosis via mitotic kinases: new opportunities for cancer managementMol Cancer Ther619201931200710.1158/1535-7163.MCT-06-078117620424
22.	K StrebhardtA UllrichTargeting polo-like kinase 1 for cancer therapyNat Rev Cancer6321330200610.1038/nrc184116557283
23.	R KnechtR ElezM OechlerC SolbachC von IlbergK StrebhardtPrognostic significance of polo-like kinase (PLK) expression in squamous cell carcinomas of the head and neckCancer Res5927942797199910383133