Skip to main content
Erschienen in: Investigational New Drugs 2/2018

30.09.2017 | SHORT REPORT

Association of Glutathione S-Transferase P-1 (GSTP-1) rs1695 polymorphism with overall survival in glioblastoma patients treated with combined radio-chemotherapy

verfasst von: Francesco Pasqualetti, Alessandra Gonnelli, Martina Cantarella, Durim Delishaj, Alessandro Molinari, Valerio Ortenzi, Francesco Carbone, Sabrina Montrone, Stefano Ursino, Sara Franceschi, Riccardo Morganti, Paola Orlandi, Teresa Di Desidero, Chiara Maria Mazzanti, Katia Zavaglia, Antonio Giuseppe Naccarato, Guido Bocci, Fabiola Paiar

Erschienen in: Investigational New Drugs | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Summary

Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults and, despite recent advances, the prognosis for this cancer remains dismal. The aims of this study were to test the influence of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms on progression free survival (PFS) and overall survival (OS) in GBM patients treated with radiotherapy (RT) and temozolomide (TMZ). Fifty GBM patients treated with upfront radio-chemotherapy (RT 60 Gy/30 sessions; TMZ 75 mg/m2 during RT and 200 mg/m2 days 1 → 5 every 28 days) were enrolled. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was used to evaluate differences between curves. A trend to a statistically significant association with PFS in univariate and multivariate COX regression analysis was found with GSTP-1 rs1695 polymorphism (p = 0.087 and p = 0.097 on univariate and multivariate analyses, respectively). Conversely, the same GSTP-1 rs1695 SNP revealed a statistically significant association with OS (p = 0.007 and p = 0.042 on univariate and multivariate analysis, respectively). Our pharmacogenetic prospective study suggests that GSTP-1 rs1695 genotypes can be associated with different OS in GBM patients treated with RT and TMZ.
Literatur
1.
Zurück zum Zitat Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, Cohen-Jonathan-Moyal E, Frappaz D, Henriksson R, Balana C, Chinot O, Ram Z, Reifenberger G, Soffietti R, Wick W, European Association for Neuro-Oncology (EANO) Task Force on Malignant Glioma (2014) EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 15(9):e395–e403CrossRefPubMed Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, Cohen-Jonathan-Moyal E, Frappaz D, Henriksson R, Balana C, Chinot O, Ram Z, Reifenberger G, Soffietti R, Wick W, European Association for Neuro-Oncology (EANO) Task Force on Malignant Glioma (2014) EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 15(9):e395–e403CrossRefPubMed
2.
Zurück zum Zitat Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996CrossRefPubMed
3.
Zurück zum Zitat Soffietti R, Trevisan E, Bertero L, Cassoni P, Morra I, Fabrini MG, Pasqualetti F, Lolli I, Castiglione A, Ciccone G, Rudà R (2014) Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology). J Neuro-Oncol 116(3):533–541CrossRef Soffietti R, Trevisan E, Bertero L, Cassoni P, Morra I, Fabrini MG, Pasqualetti F, Lolli I, Castiglione A, Ciccone G, Rudà R (2014) Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology). J Neuro-Oncol 116(3):533–541CrossRef
4.
Zurück zum Zitat Omuro A, DeAngelis LM (2013) Glioblastoma and other malignant gliomas: a clinical review. JAMA 310(17):1842–1850CrossRefPubMed Omuro A, DeAngelis LM (2013) Glioblastoma and other malignant gliomas: a clinical review. JAMA 310(17):1842–1850CrossRefPubMed
5.
Zurück zum Zitat Chinot OL, de La Motte RT, Moore N, Zeaiter A, Das A, Phillips H, Modrusan Z, Cloughesy T (2011) AVAglio: Phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme. Adv Ther 28(4):334–340CrossRefPubMed Chinot OL, de La Motte RT, Moore N, Zeaiter A, Das A, Phillips H, Modrusan Z, Cloughesy T (2011) AVAglio: Phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme. Adv Ther 28(4):334–340CrossRefPubMed
6.
Zurück zum Zitat Eisele G, Wick A, Eisele AC, Clément PM, Tonn J, Tabatabai G, Ochsenbein A, Schlegel U, Neyns B, Krex D, Simon M, Nikkhah G, Picard M, Stupp R, Wick W, Weller M (2014) Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression. J Neuro-Oncol 117(1):141–145CrossRef Eisele G, Wick A, Eisele AC, Clément PM, Tonn J, Tabatabai G, Ochsenbein A, Schlegel U, Neyns B, Krex D, Simon M, Nikkhah G, Picard M, Stupp R, Wick W, Weller M (2014) Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression. J Neuro-Oncol 117(1):141–145CrossRef
7.
Zurück zum Zitat Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, Aldape KD, Lhermitte B, Pietsch T, Grujicic D, Steinbach JP, Wick W, Tarnawski R, Nam DH, Hau P, Weyerbrock A, Taphoorn MJ, Shen CC, Rao N, Thurzo L, Herrlinger U, Gupta T, Kortmann RD, Adamska K, McBain C, Brandes AA, Tonn JC, Schnell O, Wiegel T, Kim CY, Nabors LB, Reardon DA, van den Bent MJ, Hicking C, Markivskyy A, Picard M, Weller M, European Organisation for Research and Treatment of Cancer (EORTC), Canadian Brain Tumor Consortium, CENTRIC study team (2014). Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 15(10): 1100–1108 Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, Aldape KD, Lhermitte B, Pietsch T, Grujicic D, Steinbach JP, Wick W, Tarnawski R, Nam DH, Hau P, Weyerbrock A, Taphoorn MJ, Shen CC, Rao N, Thurzo L, Herrlinger U, Gupta T, Kortmann RD, Adamska K, McBain C, Brandes AA, Tonn JC, Schnell O, Wiegel T, Kim CY, Nabors LB, Reardon DA, van den Bent MJ, Hicking C, Markivskyy A, Picard M, Weller M, European Organisation for Research and Treatment of Cancer (EORTC), Canadian Brain Tumor Consortium, CENTRIC study team (2014). Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 15(10): 1100–1108
8.
Zurück zum Zitat Sharma RA, Plummer R, Stock JK, Greenhalgh TA, Ataman O, Kelly S, Clay R, Adams RA, Baird RD, Billingham L, Brown SR, Buckland S, Bulbeck H, Chalmers AJ, Clack G, Cranston AN, Damstrup L, Ferraldeschi R, Forster MD, Golec J, Hagan RM, Hall E, Hanauske AR, Harrington KJ, Haswell T, Hawkins MA, Illidge T, Jones H, Kennedy AS, McDonald F, Melcher T, O'Connor JP, Pollard JR, Saunders MP, Sebag-Montefiore D, Smitt M, Staffurth J, Stratford IJ, Wedge SR; NCRI CTRad Academia-Pharma Joint Working Group (2016). Clinical development of new drug-radiotherapy combinations. Nat Rev Clin Oncol 13(10): 627–642 Sharma RA, Plummer R, Stock JK, Greenhalgh TA, Ataman O, Kelly S, Clay R, Adams RA, Baird RD, Billingham L, Brown SR, Buckland S, Bulbeck H, Chalmers AJ, Clack G, Cranston AN, Damstrup L, Ferraldeschi R, Forster MD, Golec J, Hagan RM, Hall E, Hanauske AR, Harrington KJ, Haswell T, Hawkins MA, Illidge T, Jones H, Kennedy AS, McDonald F, Melcher T, O'Connor JP, Pollard JR, Saunders MP, Sebag-Montefiore D, Smitt M, Staffurth J, Stratford IJ, Wedge SR; NCRI CTRad Academia-Pharma Joint Working Group (2016). Clinical development of new drug-radiotherapy combinations. Nat Rev Clin Oncol 13(10): 627–642
9.
Zurück zum Zitat Thacker J, Zdzienicka MZ (2003) The mammalian XRCC genes: their roles in DNA repair and genetic stability. DNA Repair (Amst) 2(6):655–672CrossRef Thacker J, Zdzienicka MZ (2003) The mammalian XRCC genes: their roles in DNA repair and genetic stability. DNA Repair (Amst) 2(6):655–672CrossRef
10.
Zurück zum Zitat Thacker J, Zdzienicka MZ (2004) The XRCC genes: expanding roles in DNA double-strand break repair. DNA Repair (Amst) 3(8–9):1081–1090CrossRef Thacker J, Zdzienicka MZ (2004) The XRCC genes: expanding roles in DNA double-strand break repair. DNA Repair (Amst) 3(8–9):1081–1090CrossRef
11.
Zurück zum Zitat Shridhar K, Aggarwal A, Walia GK, Gulati S, Geetha AV, Prabhakaran D, Dhillon PK, Rajaraman P (2016) Single nucleotide polymorphisms as markers of genetic susceptibility for oral potentially malignant disorders risk: Review of evidence to date. Oral Oncol 61:146–151CrossRefPubMedPubMedCentral Shridhar K, Aggarwal A, Walia GK, Gulati S, Geetha AV, Prabhakaran D, Dhillon PK, Rajaraman P (2016) Single nucleotide polymorphisms as markers of genetic susceptibility for oral potentially malignant disorders risk: Review of evidence to date. Oral Oncol 61:146–151CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Sun JF, Sui JL, Zhou PK, Geng Y, Hu YC, Cao ZS, Ge SL, Lou TZ, Wu DC (2002) Decreased efficiency of gamma-ray-induced DNA double-strand break rejoining in malignant transformants of human bronchial epithelial cells generated by alpha-particle exposure. Int J Radiat Biol 78(9):773–780CrossRefPubMed Sun JF, Sui JL, Zhou PK, Geng Y, Hu YC, Cao ZS, Ge SL, Lou TZ, Wu DC (2002) Decreased efficiency of gamma-ray-induced DNA double-strand break rejoining in malignant transformants of human bronchial epithelial cells generated by alpha-particle exposure. Int J Radiat Biol 78(9):773–780CrossRefPubMed
13.
Zurück zum Zitat Gal TJ, Huang WY, Chen C, Hayes RB, Schwartz SM (2005) DNA repair gene polymorphisms and risk of second primary neoplasms and mortality in oral cancer patients. Laryngoscope 115(12):2221–2231CrossRefPubMed Gal TJ, Huang WY, Chen C, Hayes RB, Schwartz SM (2005) DNA repair gene polymorphisms and risk of second primary neoplasms and mortality in oral cancer patients. Laryngoscope 115(12):2221–2231CrossRefPubMed
14.
Zurück zum Zitat Jin H, Xie X, Wang H, Hu J, Liu F, Liu Z, Zhou J, Zhang Y, Xi X, Hu B, Liao Y, Tang J (2014) ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma. PLoS One 9(7):e101256CrossRefPubMedPubMedCentral Jin H, Xie X, Wang H, Hu J, Liu F, Liu Z, Zhou J, Zhang Y, Xi X, Hu B, Liao Y, Tang J (2014) ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma. PLoS One 9(7):e101256CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Zhai XM, Hu QC, Gu K, Wang JP, Zhang JN, Wu YW (2016) Significance of XRCC1 Codon399 polymorphisms in Chinese patients with locally advanced nasopharyngeal carcinoma treated with radiation therapy. Asia Pac J Clin Oncol 12(1):e125–e132CrossRefPubMed Zhai XM, Hu QC, Gu K, Wang JP, Zhang JN, Wu YW (2016) Significance of XRCC1 Codon399 polymorphisms in Chinese patients with locally advanced nasopharyngeal carcinoma treated with radiation therapy. Asia Pac J Clin Oncol 12(1):e125–e132CrossRefPubMed
16.
Zurück zum Zitat Tew KD (1994) Glutathione-associated enzymes in anticancer drug resistance. Cancer Res 54(16):4313–4320PubMed Tew KD (1994) Glutathione-associated enzymes in anticancer drug resistance. Cancer Res 54(16):4313–4320PubMed
17.
Zurück zum Zitat Tew KD, Manevich Y, Grek C, Xiong Y, Uys J, Townsend DM (2011) The role of glutathione S-transferase P in signaling pathways and S-glutathionylation in cancer. Free Radic Biol Med 51(2):299–313CrossRefPubMedPubMedCentral Tew KD, Manevich Y, Grek C, Xiong Y, Uys J, Townsend DM (2011) The role of glutathione S-transferase P in signaling pathways and S-glutathionylation in cancer. Free Radic Biol Med 51(2):299–313CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Prade L, Huber R, Manoharan TH, Fahl WE, Reuter W (1997) Structures of class pi glutathione S-transferase from human placenta in complex with substrate, transition-state analogue and inhibitor. Structure 5(10):1287–1295CrossRefPubMed Prade L, Huber R, Manoharan TH, Fahl WE, Reuter W (1997) Structures of class pi glutathione S-transferase from human placenta in complex with substrate, transition-state analogue and inhibitor. Structure 5(10):1287–1295CrossRefPubMed
19.
Zurück zum Zitat Hu X, Xia H, Srivastava SK, Herzog C, Awasthi YC, Ji X, Zimniak P, Singh SV (1997) Activity of four allelic forms of glutathione S-transferase hGSTP1-1 for diol epoxides of polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun 238(2):397–402CrossRefPubMed Hu X, Xia H, Srivastava SK, Herzog C, Awasthi YC, Ji X, Zimniak P, Singh SV (1997) Activity of four allelic forms of glutathione S-transferase hGSTP1-1 for diol epoxides of polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun 238(2):397–402CrossRefPubMed
20.
Zurück zum Zitat Ishimoto TM, Ali-Osman F (2002) Allelic variants of the human glutathione S-transferase P1 gene confer differential cytoprotection against anticancer agents in Escherichia coli. Pharmacogenetics 12(7):543–553CrossRefPubMed Ishimoto TM, Ali-Osman F (2002) Allelic variants of the human glutathione S-transferase P1 gene confer differential cytoprotection against anticancer agents in Escherichia coli. Pharmacogenetics 12(7):543–553CrossRefPubMed
21.
Zurück zum Zitat Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9(5):453–461CrossRefPubMed Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9(5):453–461CrossRefPubMed
22.
Zurück zum Zitat Qi L, Yu HQ, Zhang Y, Ding LJ, Zhao DH, Lv P, Wang WY, Xu Y (2017) A Comprehensive Meta-analysis of Genetic Associations Between Key Polymorphic Loci in DNA Repair Genes and Glioma Risk. Mol Neurobiol 54(2):1314–1325CrossRefPubMed Qi L, Yu HQ, Zhang Y, Ding LJ, Zhao DH, Lv P, Wang WY, Xu Y (2017) A Comprehensive Meta-analysis of Genetic Associations Between Key Polymorphic Loci in DNA Repair Genes and Glioma Risk. Mol Neurobiol 54(2):1314–1325CrossRefPubMed
23.
Zurück zum Zitat Rapkins RW, Wang F, Nguyen HN, Cloughesy TF, Lai A, Ha W, Nowak AK, Hitchins MP, McDonald KL (2015) The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide. Neuro-Oncology 17(12):1589–1598CrossRefPubMedPubMedCentral Rapkins RW, Wang F, Nguyen HN, Cloughesy TF, Lai A, Ha W, Nowak AK, Hitchins MP, McDonald KL (2015) The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide. Neuro-Oncology 17(12):1589–1598CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Franceschi S, Tomei S, Mazzanti CM, Lessi F, Aretini P, La Ferla M, De Gregorio V, Pasqualetti F, Zavaglia K, Bevilacqua G, Naccarato AG (2016) Association between RAD 51 rs1801320 and susceptibility to glioblastoma. J Neuro-Oncol 126(2):265–270CrossRef Franceschi S, Tomei S, Mazzanti CM, Lessi F, Aretini P, La Ferla M, De Gregorio V, Pasqualetti F, Zavaglia K, Bevilacqua G, Naccarato AG (2016) Association between RAD 51 rs1801320 and susceptibility to glioblastoma. J Neuro-Oncol 126(2):265–270CrossRef
25.
Zurück zum Zitat Pasqualetti F, Orlandi P, Simeon V, Cantarella M, Giuliani D, Di Desidero T, Gonnelli A, Delishaj D, Lombardi G, Sechi A, Sanson M, Zagonel V, Paiar F, Danesi R, Guarini S, Bocci G (2017) Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy. Mol Neurobiol. https://doi.org/10.1007/s12035-017-0414-9 Pasqualetti F, Orlandi P, Simeon V, Cantarella M, Giuliani D, Di Desidero T, Gonnelli A, Delishaj D, Lombardi G, Sechi A, Sanson M, Zagonel V, Paiar F, Danesi R, Guarini S, Bocci G (2017) Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy. Mol Neurobiol. https://​doi.​org/​10.​1007/​s12035-017-0414-9
26.
Zurück zum Zitat Sullivan I, Salazar J, Majem M, Pallarés C, Del Río E, Páez D, Baiget M, Barnadas A (2014) Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. Cancer Lett 353(2):160–166CrossRefPubMed Sullivan I, Salazar J, Majem M, Pallarés C, Del Río E, Páez D, Baiget M, Barnadas A (2014) Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. Cancer Lett 353(2):160–166CrossRefPubMed
27.
Zurück zum Zitat Leguisamo NM, Gloria HC, Kalil AN, Martins TV, Azambuja DB, Meira LB, Saffi J (2017). Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy. Oncotarget 8(33):54199-54214 Leguisamo NM, Gloria HC, Kalil AN, Martins TV, Azambuja DB, Meira LB, Saffi J (2017). Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy. Oncotarget 8(33):54199-54214
28.
Zurück zum Zitat Muñoz C, Caballero M, Hakim S, Verger E, Grau JJ (2016) Influence of allelic Variations of hypoxia-related and DNA repair genes on patient outcome and toxicity in head and neck cancer treated with radiotherapy plus cetuximab. Eur Arch Otorhinolaryngol 273(8):2193–2199CrossRefPubMed Muñoz C, Caballero M, Hakim S, Verger E, Grau JJ (2016) Influence of allelic Variations of hypoxia-related and DNA repair genes on patient outcome and toxicity in head and neck cancer treated with radiotherapy plus cetuximab. Eur Arch Otorhinolaryngol 273(8):2193–2199CrossRefPubMed
29.
Zurück zum Zitat Liu HF, Liu JS, Deng JH, Wu RR (2016) Role of XRCC1 gene polymorphisms in non-small cell lung cancer cisplatin-based chemotherapy, and their effect on clinical and pathological characteristics. Genet Mol Res 15(4). https://doi.org/10.4238/gmr15049084 Liu HF, Liu JS, Deng JH, Wu RR (2016) Role of XRCC1 gene polymorphisms in non-small cell lung cancer cisplatin-based chemotherapy, and their effect on clinical and pathological characteristics. Genet Mol Res 15(4). https://​doi.​org/​10.​4238/​gmr15049084
30.
Zurück zum Zitat Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003CrossRefPubMed Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003CrossRefPubMed
Metadaten
Titel
Association of Glutathione S-Transferase P-1 (GSTP-1) rs1695 polymorphism with overall survival in glioblastoma patients treated with combined radio-chemotherapy
verfasst von
Francesco Pasqualetti
Alessandra Gonnelli
Martina Cantarella
Durim Delishaj
Alessandro Molinari
Valerio Ortenzi
Francesco Carbone
Sabrina Montrone
Stefano Ursino
Sara Franceschi
Riccardo Morganti
Paola Orlandi
Teresa Di Desidero
Chiara Maria Mazzanti
Katia Zavaglia
Antonio Giuseppe Naccarato
Guido Bocci
Fabiola Paiar
Publikationsdatum
30.09.2017
Verlag
Springer US
Erschienen in
Investigational New Drugs / Ausgabe 2/2018
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-017-0516-2

Weitere Artikel der Ausgabe 2/2018

Investigational New Drugs 2/2018 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.