The Pharmacology laboratory focuses on how to implement personalized treatment into the clinic. Major approaches include the use of pharmacogenetics and pharmacogenomics to determine whether patients will respond to a drug or drug combination. The current research lines focus on the interaction between drugs targeted against DNA and against signal transduction cascades in tumor cells. Elucidation of resistance mechanisms to novel drugs and on ways to bypass them is studied both in appropriate model systems and in patients.
The Pharmacology Research group in August 2009.
Upper row: Frits Peters , Nienke Losekoot, Kees Smid, Letizia Porcelli, Richard Honeywell, Irene Bijnsdorp, Leonie de Wilt; sitting: Ietje Kathman, Claudia Alecci, Kaamar Azijli, Elisa Giovannetti , Leticia Leon
The laboratory has a long-standing history in translational research. More than half of the Ph.D. students have a medical background and several of them are now involved in translational research at the VU University Medical Center and elsewhere. The translational research has led to the successful introduction into the clinic of several drugs and concepts (co)-developed in the department. This includes the role of thymidylate synthase in the efficacy of fluoro-pyrimidines (e.g. 5-FU and capecitabine) and antifolates (e.g. pemetrexed), optimization of gemcitabine treatment with cisplatin (development of the cisplatin-gemcitabine combination) and more recently the role of EGFR mutations and expression in the efficacy of EGFR inhibitors.
Some recent research highlights
Recently several major interests merged into a novel concept of drug resistance. Resistance to many anticancer drugs has been associated with increased efflux of a drug out of the cell, the so-called multidrug-resistance (MDR). This efflux is energy dependent and hence requires ATP. One of these pumps, ABCG2, initially called Breast Cancer Resistance Protein (BCRP), was associated with resistance to drugs such as mitoxantrone, but also several novel antifolates such as pemetrexed. Jan-Hendrik Hooijberg and Clara Lemos demonstrated that the sensitivity of the latter drugs is also dependent on the folate homeostasis of the cell and the body; proper folate supplementation enhances the antitumor activity and protects normal tissues from antifolate toxicity. Unexpectedly, folate depletion also affected the sensitivity to EGFR tyrosine kinase inhibitors such as gefitinib and erlotinib. This could be explained by an upregulation of BCRP in these cells. Clara Lemos demonstrated that the localization of BCRP was not on the cellular membrane but intracellularly, a process possibly regulated by phosphorylation of essential serine-threonine and tyrosine kinases. This phenomenon may influence the efficacy of other novel receptor tyrosine kinase inhibitors as well. Current research therefore focuses on the role of efflux pumps on the sensitivity of novel tyrosine kinase inhibitors and their effect in cellular uptake using novel sensitive techniques such as LC coupled to mass spectrometry.
The novel proteasome inhibitor bortezomib was studied intensively for its interaction with standard chemotherapy (gemcitabine-cisplatin) in non-small cell lung cancer. Elisa Giovannetti and Richard Honeywell demonstrated that bortezomib prevented gemcitabine activation in normal white blood cells but selectively enhanced its activation in tumor cells, by preventing the degradation of the key activation enzyme of gemcitabine, deoxycytidine kinase. In a collaborative Italian study, Elisa Giovannetti demonstrated that the antitumor activity and toxicity of gemcitabine are related to a specific polymorphism in the degradation enzyme of gemcitabine, deoxycytidine deaminase. Prospective studies on the role of dCDA to select patients are warranted. Careful analysis of a similar group of patients by Mariëlle Gallegos Ruiz and Elisa Giovannetti also revealed that signal transduction pathways downstream of EGFR may play a similar or even more important role in the efficacy of these drugs.
2012
Phillips RM, Hendriks HR, Peters GJ; on behalf of the EORTC-Pharmacology and Molecular Mechanism Group. EO9 (Apaziquone): From the clinic to the laboratory and back again. Br J Pharmacol 2012 Apr 18. doi: 10.1111/j.1476-5381.2012.01996.x. [Epub ahead of print].
Kaye S, Aamdal S, Jones R, Freyer G, Pujade-Lauraine E, de Vries EG, Barriuso J, Sandhu S, Tan DS-W, Hartog V, Kuenen B, Ruijter R, Kristensen GB, Nyakas M, Barrett S, Burke W, Pietersma D, Stuart M, Emeribe U, Boven E. Phase I study of saracatinib (AZD0530) in combination with paclitaxel and/or carboplatin in patients with solid tumours. Br J Cancer 2012; advance online publication, April 24, 2012; doi:10.1038/bjc.2012.158.
Muggia F, Diaz I, Peters GJ. Nucleoside and nucleobase analogs in cancer treatment: not only sapacitabine, but also gemcitabine. Exp Opin Investig Drugs 2012; 21: 403-408.
Elnaggar M, Giovannetti E, Peters GJ. Molecular targets of gemcitabine action: rationale for development of novel drugs and drug combinations. Curr Pharm Des 2012 Feb 28. [Epub ahead of print].
Giovannetti E, Codacci-Pisanelli G, Peters GJ. TFAP2E-DKK4 and chemoresistance in colorectal cancer. New Engl J Med 2012; 366: 966; author reply 966.
Peccatori FA, Giovannetti E, Pistilli B, Bellettini G, Codacci-Pisanelli G, Losekoot N, Curigliano G, Azim HA Jr, Goldhirsch A, Peters GJ. "The only thing I know is that I know nothing": 5-fluorouracil in human milk. Ann Oncol 2012; 23: 543-544.
Verbrugge SE, Assaraf YG, Dijkmans BA, Scheffer GL, Al M, den Uyl D, Oerlemans R, Chan ET, Kirk CJ, Peters GJ, van der Heijden JW, de Gruijl TD, Scheper RJ, Jansen G. Inactivating PSMB5 mutations and P-glycoprotein (MDR1/ ABCB1) mediate resistance to proteasome inhibitors: ex vivo efficacy of (immuno) proteasome inhibitors in mononuclear blood cells from rheumatoid arthritis patients. J Pharmacol Exp Ther 2012; 341: 174-182.
de Wilt LHAM, Jansen G, Assaraf YG, van Meerlood J, Cloos J, Schimmer AD, Chan ET, Kirk CJ, Peters GJ, Kruyt FAE. Proteasome-based mechanisms of intrinsic and acquired bortezomib resistance in non-small cell lung cancer. Biochem Pharmacol 2012; 83: 207-217.
Adema AD, Smid K, Losekoot N, Honeywell RJ, Verheul HM, Myhren F, Sandvold ML, Peters GJ. Metabolism and accumulation of the lipophilic deoxynucleoside analogs elacytarabine and CP-4126. Invest New Drugs 2011; 2011 Oct 15. [Epub ahead of print].
Tibaldi C, Giovannetti E, Tiseo M, Leon LG, D'Incecco A, Loosekoot N, Bartolotti M, Honeywell R, Cappuzzo F, Ardizzoni A, Peters GJ. Correlation of cytidine deaminase polymorphisms and activity with clinical outcome in gemcitabine-/platinum-treated advanced non-small-cell lung cancer patients. Ann Oncol 2012; 23: 670-677.
Giovannetti E, Erozenci A, Smit J, Danesi R, Peters GJ. Molecular mechanisms underlying the role of microRNAs (miRNAs) in anticancer drug resistance and implications for clinical practice. Crit Rev Oncol Hematol 2012; 81: 103-122.
2011
Hodzic J, Giovannetti E, Calvo BD, Adema AD, Peters GJ. Regulation of deoxycytidine kinase expression and sensitivity to gemcitabine by micro-RNA 330 and promoter methylation in cancer cells. Nucleosides Nucleotides Nucleic Acids 2011; 30:1214-2122.
Honeywell RJ, Giovannetti E, Peters GJ. Determination of the phosphorylated metabolites of gemcitabine and of difluorodeoxyuridine by LCMSMS.
Nucleosides Nucleotides Nucleic Acids 2011; 30:1203-1213.
Bijnsdorp IV, Peters GJ. Deoxyribose protects against rapamycin-induced cytotoxicity in colorectal cancer cells in vitro. Nucleosides Nucleotides Nucleic Acids 2011; 30:1197-1202.
Peters GJ, Adema AD, Bijnsdorp IV, Sandvold ML. Lipophilic prodrugs and formulations of conventional (deoxy)nucleoside and fluoropyrimidine analogs in cancer. Nucleosides Nucleotides Nucleic Acids 2011; 30:1168-1180.
Giovannetti E, Pacetti P, Reni M, Leon LG, Mambrini A, Vasile E, Ghidini M, Funel N, Lucchesi M, Cereda S, Peters GJ, Cantore M. Association between DNA-repair polymorphisms and survival in pancreatic cancer patients treated with combination chemotherapy. Pharmacogenomics 2011; 12:1641-1652.
Gotink KJ, Broxterman HJ, Labots M, de Haas RR, Dekker H, Honeywell RJ, Rudek MA, Beerepoot LV, Musters RJ, Jansen G, Griffioen AW, Assaraf YG, Pili R, Peters GJ, Verheul HMW. Lysosomal sequestration of sunitinib: a novel mechanism of drug resistance. Clin Cancer Res 2011; 17: 7337-7346.
Giovannetti E, Zucali PA, Assaraf YG, Leon LG, Smid K, Alecci C, Giancola F, Destro A, Gianoncelli L, Lorenzi E, Roncalli M, Santoro A, Peters GJ. Pre-clinical emergence of vandetanib as a potent antitumour agent in meso-thelioma: molecular mechanisms underlying its synergistic interaction with pemetrexed and carboplatin. Br J Cancer 2011; 105: 1542-1553.
Granchi C, Roy S, De Simone A, Salvetti I, Tuccinardi T, Martinelli A, Macchia M, Lanza M, Betti L, Giannaccini G, Lucacchini A, Giovannetti E, Sciarrillo R, Peters GJ, Minutolo F. N-Hydroxyindole-based inhibitors of lactate dehydrogenase against cancer cell proliferation. Eur J Med Chem 2011; 46: 5398-5407.
Galvani E, Peters GJ, Giovannetti E. Thymidylate synthase inhibitors for non-small cell lung cancer. Exp Opin Investig Drugs 2011; 20:1343-1356.
Funel N, Giovannetti E, Pollina LE, Del Chiaro M, Mosca F, Boggi U, Campani D. Critical role of laser microdissection for genetic, epigenetic and proteomic analyses in pancreatic cancer. Expert Rev Mol Diagn 2011; 11:695-701.
Rekers NH, Sminia P, Peters GJ. Towards tailored therapy of glioblastoma multiforme. J Chemother 2011; 23:187-199.
Leon LG, Giovannetti E, Smid K, van Houte BP, Hanauske AR, Giaccone G, Peters GJ. DNA copy number profiles correlate with outcome in colorectal cancer patients treated with fluoropyrimidine/antifolate-based regimens. Curr Drug Metabol 2011; 12: 956-965.
Porcelli L, Assaraf YG, Azzariti A, Paradiso A, Jansen G, Peters GJ. The impact of folate status on the efficacy of colorectal cancer treatment. Curr Drug Metabol 2011; 12: 975-984.
Broekman F, Giovannetti E, Peters GJ. Tyrosine kinase inhibitors: Multi-targeted or single-targeted? World J Clin Oncol 2011; 2:80-93.
Rajendra Prasad VV, Peters GJ, Lemos C, Kathmann I, Mayur YC. Cytotoxicity studies of some novel fluoro acridone derivatives against sensitive and resistant cancer cell lines and their mechanistic studies. Eur J Pharm Sci 201; 43:217-224.
Bijnsdorp IV, Giovannetti E, Peters GJ. Analysis of drug interactions. Methods Mol Biol 2011; 731:421-434.
León LG, Giovannetti E, Alecci C, Giancola F, Funel N, Zucali P, Peters GJ, Padrón JM. Antiproliferative effects of novel aliphatic acetogenin analogs against aggressive solid tumor cell lines. In vivo 2011; 25:203-207.
Bijnsdorp IV, Capriotti F, Kruyt FAE, Losekoot N, Fukushima M, Griffioen AW, Thijssen VL, Peters GJ. Thymidine phosphorylase in cancer cells stimulates human endothelial cell migration and invasion by the secretion of angiogenic factors. Br J Cancer 2011; 104: 1185-1192.
Jharap B, de Boer NK, Vos RM, Smid K, Zwiers A, Peters GJ, Mulder CJ, Wilhelm AJ, van Bodegraven AA. Biotransformation of 6-thioguanine in inflammatory bowel disease patients: a comparison of oral and intravenous administration of 6-thioguanine. Br J Pharmacol 2011; 163:722-731.
Granchi C, Roy S, Giacomelli C, Macchia M, Tuccinardi T, Martinelli A, Lanza M, Betti L, Giannaccini G, Lucacchini A, Funel N, Leo´n LG, Giovannetti E, Peters GJ, Palchaudhuri R, Calvaresi EC, Hergenrother PJ, Minutolo F. Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells. J Med Chem 2011; 54: 1599-1612.
Lemos C, Giovannetti E, Zucali PA, Assaraf YG, Scheffer GL, van der Straaten T, D'Incecco A, Falcone A, Guchelaar HJ, Danesi R, Santoro A, Giaccone G, Tibaldi C, Peters GJ. Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients. Pharmaco-genomics 2011; 12:159-170.
Zucali PA, Giovannetti E, Destro A, Mencoboni M, Ceresoli GL, Gianoncelli L, Lorenzi E, De Vincenzo F, Simonelli M, Perrino M, Bruzzone A, Thunnissen E, Tunesi G, Giordano L, Roncalli M, Peters GJ, Santoro A. Thymidylate synthase and excision repair-cross-complementing group-1 as predictors of responsiveness in mesothelioma patinets treated with premetrexed-carboplatin. Clin Cancer Res 2011; 17:2581-2590.
Tibaldi C, Giovannetti E, Vasile E, Boldrini L, Gallegos-Ruiz MI, Bernardini I, Incensati R, Danesi R, Cappuzzo F, Peters GJ, Fontanini G. Inherited germline T790M mutation and somatic epidermal growth factor receptor mutations in non-small cell lung cancer patients. J Thorac Oncol 2011; 6:395-396.
Jacobs H, Bast A, Peters GJ, van der Vijgh WJF, Haenen GRM. The semi-synthetic flavonoid monoHER sensitises human soft tissue sarcoma cells to doxorubicin-induced apoptosis via inhibition of nuclear factor-kB. Br J Cancer 2011; 104:437-440.
Giovannetti E, Erdem L, Olcay E, Leon LG, Peters GJ. Influence of polymorphisms on EGFR targeted therapy in non-small-cell lung cancer. Front Biosci 2011; 16:116-130.
2010
Pastina I, Giovannetti E, Chioni A, Sissung TM, Crea F, Orlandini C, Price DK, Cianci C, Figg WD, Ricci S, Danesi R. Cytochrome 450 1B1 (CYP1B1) polymorphisms associated with response to docetaxel in castration-resistant prostate cancer (CRPC) patients. BMC Cancer 2010 Sep 27;10:511.
Toffalorio F, De Pas T, Giovannetti E. Differences of gene expression in non-small cell lung cancer: are histology, tumor site, and methodology relevant? J Thorac Oncol 2010 Aug;5(8):1310-1; author reply 1311.
Schneiders FL, van den Berg HP, Peters GJ, Verheul HM, van der Vliet HJ. Severe toxicity of capecitabine following uncomplicated treatment with 5-fluorouracil/leucovorin. Med Oncol 2010; Jun 22 [Epub ahead of print].
Bijnsdorp IV, Azijlia K, Jansen EE, Wamelink MM, Jakobs C, Struys EA, Fukushima M, Kruyt FAE, Peters GJ. Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells. Biochem Pharmacol 2010; 80:786-792.
Hwang JH, Voortman J, Giovannetti E, Steinberg SM, Leon LG, Kim YT, Funel N, Park JK, Kim MA, Kang GH, Kim SW, Del Chiaro M, Peters GJ, Giaccone G. Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer. Plos One 2010; May 14;5(5):e10630.
Giovannetti E, Funel N, Peters GJ, Del Chiaro M, Erozenci LA, Vasile E, Leon LG, Pollina LE, Groen A, Falcone A, Danesi R, Campani D, Verheul HM, Boggi U. MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res 2010; 70:4528-4538.
Sigmond J, Bergman AM, Leon LG, Loves WJ, Hoebe EK, Peters GJ. Staurosporine increases toxicity of gemcitabine in non-small cell lung cancer cells: role of protein kinase C, deoxycytidine kinase and ribonucleotide reductase. Anticancer Drugs 2010; 21:591-599.
Zucali PA, Giovannetti E, Assaraf YG, Ceresoli GL, Peters GJ, Santoro A. New tricks for old biomarkers: thymidylate synthase expression as a predictor of pemetrexed activity in malignant mesothelioma. Ann Oncol 2010; 21:1560-1561.
Lind JSW, Dingemans AC, Groen HJM, Thunnissen E, Bekers O, Heideman DAH, Honeywell R, Giovannetti E, Peters GJ, Postmus PE, van Suylen RJ, Smit EF. A Multicenter, Phase II study of erlotinib and sorafenib in chemotherapy-naïve patients with advanced non-small cell lung cancer. Clin Cancer Res 2010; 16:3078-3087.
Honeywell R, Yarzadah K, Giovannetti E, Losekoot N, Smit EF, Walraven M, Lind JS, Tibaldi C, Verheul HM, Peters GJ. Simple and selective method for the determination of various tyrosine kinase inhibitors used in the clinical setting by liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2010; 878:1059-1068.
Temmink OH, Bijnsdorp IV, Prins HJ, Losekoot N, Adema AD, Smid K, Honeywell RJ, Ylstra B, Eijk PP, Fukushima M, Peters GJ. Trifuorothyimidine resistance is associated with decreased thymidine kinase and equilibrative nucleoside transporter expression or increased secretory phospholipase A2. Mol Cancer Ther 2010; 9:1047-1057.
Giovannetti E, Tibaldi C, Falcone A, Danesi R, Peters GJ. Impact of cytidine deaminase polymorphisms on toxicity after gemcitabine: the question is still ongoing. J Clin Oncol 2010; 28:e221-222; author reply e223-225.
Bergman AM, Adema AD, Balzarini J, Bruheim S, Fichtner I, Noordhuis P, Fodstad O, Myhren F, Sandvold ML, Hendriks HR, Peters GJ. Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models. Invest New Drugs 2010; in press.
Bijnsdorp IV, Schwendener RA, Schott H, Fichtner I, Smid K, Laan AC, Schott S, Losekoot N, Honeywell RJ, Peters GJ. Cellular pharmacology of multi- and duplex drugsconsisting of ethynylcytidine and 5-fluoro-2'-deoxyuridine. Invest New Drugs 2010; 2009 Dec 3. [Epub ahead of print].
Giovannetti E, Zucali PA, Peters GJ, Cortesi F, D'Incecco A, Smit EF, Falcone A, Burgers JA, Santoro A, Danesi R, Giaccone G, Tibaldi C. Association of polymorphisms in AKT1 and EGFR with clinical outcome and toxicity in non-small cell lung cancer patients treated with gefitinib. Mol Cancer Ther 2010; 9: 581-593.
Adema AD, Laan AC, Myhren F, Fichtner I, Verheul HM, Sandvold ML, Peters GJ. Cell cycle effects of fatty acid derivatives of cytarabine, CP-4055, and of gemcitabine, CP-4126, as basis for the interaction with oxaliplatin and docetaxel. Int J Oncol 2010; 36: 285-294.
Bijnsdorp IV, Kruyt FA, Fukushima M, Smid K, Gokoel S, Peters GJ. Molecular mechanism underlying the synergistic interaction between trifluorothymidine and the epidermal growth factor receptor inhibitor erlotinib in human colorectal cancer cell lines. Cancer Sci 2010; 101: 440-447.
Bijnsdorp IV, Peters GJ, Temmink OH, Fukushima M, Kruyt FA. Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5-fluorouracil in colon cancer cells. Int J Cancer 2010; 126: 2457-2468.
Giovannetti E, Honeywell R, Hanauske AR, Tekle C, Kuenen B, Sigmond J, Giaccone G, Peters GJ. Pharmacological aspects of the enzastaurin-pemetrexed combination in non-small cell lung cancer (NSCLC). Current Drug Targets 2010; 11: 12-28.
2009
Sigmond J, Honeywell RJ, Postma TJ, Dirven CMF, De Lange SM, Van der Born K, Laan AC, Baayen JC, Van Groeningen CJ, Bergman AM, Giaccone G, Peters GJ. Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer. Ann Oncol 2009; 20: 182-187.
Gallegos Ruiz MI, Floor K, Steinberg SM, Grünberg K, Thunnissen FBJM, Belien JAM, Meijer GA, Peters GJ, Smit EF, Rodriguez JA, Giaccone G (2009). Combined assesment of EGFR pathway-related molecular markers and prognosis of NSCLC patients. Br J Cancer 2009; 100: 145-152.
Porcelli L, Lemos C, Peters GJ, Paradiso A, Azzariti A. Intracellular trafficking of MDR transporters and relevance of SNPs. Current Topics Med Chem 2009; 9: 197-208.
Lemos C, Kathmann I, Giovannetti E, Beliën J, Scheffer GL, Calhau C, Jansen G, Peters GJ. Cellular folate status modulates the expression of BCRP and MRP multidrug transporters in cancer cell lines from different origins. Mol Cancer Ther 2009; 8: 655-664.
De Jonge R, Tissing W, Hooijberg JH, Jansen G, Kaspers GJL, Lindemans J, Peters GJ, Pieters R. Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. Blood 2009; 113: 2284-2289.
Lemos C, Kathmann I, Giovannetti E, Calhau, C, Jansen G, Peters GJ. Impact of cellular folate status and epidermal growth factor receptor-expressing cells on BCRP/ABCG2 mediated resistance to gefitinib and erlotinib. Br J Cancer 2009; 100: 1120-1127.
Muggia FM, Peters GJ, Landolph Jr, JR (2009). XIII International Charles Heidelberger Symposium and 50 Years of Fluoropyrimidines in Cancer Therapy Held on September 6 to 8, 2007 at New York University Cancer Institute,Smilow Conference Center. Mol Cancer Ther. 2009; 8: 992-999.
Ceresa C, Giovannetti E, Voortman J, Laan AC, Honeywell R, Giaccone G, Peters GJ. Bortezomib induces schedule-dependent modulation of gemcitabine pharmacokinetics and pharmacodynamics in non-small cell lung cancer and blood mononuclear cells. Mol. Cancer Ther. 2009; 8: 1026-1036.
Fotoohi AK, Assaraf YG, Moshfegh A, Hashemi J, Jansen G, Peters GJ, Larsson C, Albertioni F. Gene expression profiling of leukemia T-cells resistant to methotrexate and 7-hydroxymethotrexate reveals alterations that preserve intracellular levels of folate and nucleotide biosynthesis. Biochem. Pharmacol. 2009; 77: 1410-1417.
Mayur YC, Peters GJ, Prasad VVSR, Lemos C, Sathish NK. Design of new drug molecules to be used in reversing multdrug resistance in cancer cells. Current Cancer Drug Targets 2009; 9: 298-306.
Andersson R, Aho U, Nilsson BI, Peters GJ, Pastor-Anglada M, Rasch W, Sandvold ML. Gemcitabine chemoresistance in pancreatic cancer: molecular mechanisms and potential solutions. Scand J Gastroenterol 2009; 44: 782-786.
Mauritz R, Giovannetti E, Beumer IJ, Smid K, Van Groeningen CJ, Pinedo HM, Peters GJ. Polymorphisms in the enhancer region of the thymidylate synthase gene are associated with thymidylate synthase levels in normal tissues but not in malignant tissues of patients with colorectal cancer. Clin Colorectal Cancer 2009; 8: 146-154.
Adema AD, Van der Born K, Honeywell RJ, Peters GJ. Cell cycle effects and increased adduct formation by temozolomide enhance the effect of cytotoxic and targeted agents in lung cancer cell lines. J Chemotherapy 2009; 21: 338-346.
Postma C, Koopman M, Buffart TE, Eijk PP, Carvalho B, Peters GJ, Ylstra B, van Krieken JH, Punt CJ, Meijer GA(2009). DNA copy number profiles of primary tumors as predictors of response to chemotherapy in advanced colorectal cancer. Ann Oncol. 20; 1048-1056.
Crea F, Giovannetti E, Cortesi F, Mey V, Nannizzi S, Gallegos Ruiz MI, Ricciardi S, Del Tacca M, Peters GJ, Danesi R. Epigenetic mechanisms of irinotecan sensitivity in colorectal cancer cell lines. Mol Cancer Ther 2009; 8: 1964-1973.
Van Riel JM, Peters GJ, Mammatas LH, Honeywell RJ, Laan AC, Ruyter R, Van den Berg F, Giaccone G, Van Groeningen CJ. A phase I and pharmacokinetic study of gemcitabine given by 24-hour hepatic arterial infusion. Eur J Cancer 2009; 45: 2519-2526.
Adema AD, Bijnsdorp IV, Sandvold ML, Verheul HM, Peters GJ. Innovations and opportunities to improve conventional (deoxy)nucleoside and fluoropyrimidine analogs in cancer. Current Med Chem 2009; 16: 4632-4643.
Mayur YC, Zaheeruddin, Peters GJ, Lemos C, Kathmann I, Rajendra Prasad VVS. Synthesis of 2-fluoro N10-substituted acridones and their cytotoxicity studies in sensitive and resistant cancer cell lines and their DNA intercalation studies. Archiv Pharmazie 2009; 342: 640-650.
2008
Giovannetti E, Ugrasena DG, Supriyadi E, Vroling L, Azzarello A, De Lange D, Peters GJ, Veerman AJP, Cloos J. Methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase promoter (TSER) polymorphisms in Indonesian children with and without leukemia. Leuk Res 2008; 32: 19-24.
Lemos C, Jansen G, Peters GJ. Drug transporters: recent advances concerning BCRP and tyrosine kinase inhibitors. Br J Cancer 2008; 98: 857-862.
Tibaldi C, Giovannetti E, Vasile E, Mey V, Laan AC, Nannizzi S, Di Marsico R, Antonuzzo A, Orlandini C, Ricciardi S, Del Tacca M, Peters GJ, Falcone A, Danesi R. Correlation of cytidine deaminase, ercc1 and xpd polymorphisms with response and survival in gemcitabine/cisplatin-treated advanced non-small-cell lung cancer patients. Clin Cancer Res. 2008; 14: 1797-803.
Giovannetti E , Lemos C, Tekle C , Smid K, Nannizi S, Rodriguez JA, Ricciardi S, Danesi R, Giaccone G, Peters GJ. Molecular mechanisms underlying the synergistic interaction of erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, with the multitargeted antifolate pemetrexed in non-small-cell lung cancer cells. Mol Pharmacol 2008; 73: 1290-300.
Noordhuis P, Laan AC, Van der Born K, Losekoot N, Kathmann I, Peters GJ. Oxaliplatin activity in selected and unselected human ovarian and colorectal cancer cell lines. Biochem. Pharmacol. 2008; 76: 63-71.
Staffhorst RWHM, Van der Born K, Erkelens CAM, Hamelers IHL, Peters GJ, Boven E, De Kroon AIPM. Antitumor activity and biodistribution of cisplatin nanocapsules in nude mice bearing ovarian carcinoma xenografts. Anticancer Drugs 2008;19: 721-727.
Lemos C, Kathmann I, Giovannetti E, Dekker H, Scheffer GL, Calhau C, Jansen G, Peters GJ (2008). Folate deprivation induces BCRP (ABCG2) expression and mitoxantrone resistance in Caco-2 cells. Int J Cancer 2008; 123: 1712-1717.
Direcks WGE, Berndsen SC, Proost N, Peters GJ, Balzarini J, Spreeuwenberg, MD, Lammertsma AA, Molthoff CFM. [18F]FDG and [18F]FLT uptake in human breast cancer cells in relation to the effects of chemotherapy: an in vitro study. Br J Cancer 2008; 99: 481-487.
Tekle C, Giovannetti E, Sigmond J, Graff JR, Smid K, Peters GJ. Molecular pathways involved in the synergistic interaction of the PKCß inhibitor enzastaurin with the antifolate pemetrexed in non-small cell lung cancer cell lines. Br J Cancer 2008; 99: 750-759.
Mauritz R, Peters GJ, Kathmann I, Teshale H, Noordhuis P, Comijn EM, Pinedo HM, Jansen G. Dynamics of antifolate transport via the reduced folate carrier and the membrane folate receptor in murine leukaemia cells in vitro and in vivo. Cancer Chemother Pharmacol 2008; 62: 937-948.
Bijnsdorp IV, Kruyt FAE, Gokoel S, Fukushima M, Peters GJ. Synergistic interaction of trifluorothymidine with docetaxel (Taxotere®) after sequential scheduling. Cancer Sci 2008; 99: 2302-2309.