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| 1 | Metastatic pancreatic cancer: Is there a light at the end of the tunnel?显示文摘Due to extremely poor prognosis,pancreatic cancer(PDAC)represents the fourth leading cause of cancerrelated death in Western countries.For more than a decade,gemcitabine(Gem)has been the mainstay of first-line PDAC treatment.Many efforts aimed at improving single-agent Gem efficacy by either combining it with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation provided disappointing results.Recently,the field of systemic therapy of advanced PDAC is finally moving forward.Polychemotherapy has shown promise over single-agent Gem:regimens like PEFG-PEXG-PDXG and GTX provide significant potential advantages in terms of survival and/or disease control,although sometimes at the cost of poor tolerability.The PRODIGE 4/ACCORD 11 was the first phaseⅢtrial to provide unequivocal benefit using the polychemotherapy regimen FOLFIRINOX;however the less favorable safety profile and the characteristics of the enrolled population,restrict the use of FOLFIRINOX to young and fit PDAC patients.The nanoparticle albumin-bound paclitaxel(nab-Paclitaxel)formulation was developed to overcome resistance due to the desmoplastic stroma surrounding pancreatic cancer cells.Regardless of whether or not this is its main mechanisms of action,the combination of nabPaclitaxel plus Gem showed a statistically and clinically significant survival advantage over single agent Gem and significantly improved all the secondary endpoints.Furthermore,recent findings on maintenance therapy are opening up potential new avenues in the treatment of advanced PDAC,particularly in a new era in which highly effective first-line regimens allow patients to experience prolonged disease control.Here,we provide an overview of recent advances in the systemic treatment of advanced PDAC,mostly focusing on recent findings that have set new standards in metastatic disease.Potential avenues for further development in the metastatic setting and current efforts to integratenew effective chemotherapy regimens in earlier stages of disease(neoadjuvant,adjuvant,and multimodal approaches in both resectable and unresectable patients)are also briefly discussed. | Vanja Vaccaro Isabella Sperduti Sabrina Vari Emilio Bria Davide Melisi Carlo Garufi Carmen Nuzzo Aldo Scarpa Giampaolo Tortora Francesco Cognetti Michele Reni Michele Milella | 2015 | World Journal of Gastroenterology2015，21，16： | 2 |
| 2 | Oral poly(ADP-ribose) polymerase-1 inhibitor BSI-401 has antitumor activity and synergizes with oxaliplatin against pancreatic cancer, preventing acute neurotoxicity 显示文摘 | Melisi D | 2009 | Clin Cancer Res2009，15，20： | 1 |
| 3 | NF-κB as a target for pancreatic cancer thera- py显示文摘 | Carbone C Melisi D | 2012 | Expert Opin Ther Targets2012，16，2： | 1 |
| 4 | LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis 显示文摘 | MELISI D ISHIYAMA S SCLABAS G M | 2008 | Mol Cancer Ther2008，7，4： | 1 |
| 5 | Angiogenesis:a target for cancer therapy显示文摘 | Tortora G Melisi D Ciardiello F | 2004 | Curr Pharm Des2004，10，1： | 1 |
| 6 | Emerging pathways and future targets for the molecular therapy of pancreatic cancer显示文摘 | VACCARO V MELISI D BRIA E | 2011 | Expert Opin Ther Targets2011，15，10： | 1 |
| 7 | NF -κB as a target for pancreatic cancer therapy显示文摘 | CARBONE C MELISI D | 2012 | Expert Opin Ther Targets2012，16，2： | 1 |
| 8 | Key cancer cell signal transduction pathways as therapeutic targets显示文摘 | Bianco R Melisi D Ciardiello F | 2006 | Eur J Cancer2006，42，3： | 1 |
| 9 | Modulation of pancreatic cancer chemoresistance by inhibition of TAK1 显示文摘 | Melisi D Xia Q Paradiso G | 2011 | J Natl CancerInst2011，103，15： | 1 |
| 10 | Key cancer ce-ll signal transduction pathways as therapeutic targets显示文摘 | Bianeo R Melisi D Ciardiello F | | 0，，03： | 1 |
| 11 | Key cancer cell signal transduction pathways as therapeutic targets显示文摘 | BIANCO R MELISI D CIARDIELLO F | 2006 | Eur J Cancer2006，42，3： | 1 |
| 12 | Secreted interleukin-1 alpha induces a metastatic phenotype in pancreatic cancer by sustaining a constitutive activation of nuclear factor-kappaB显示文摘 | MELISI D NIU Jiangong CHANG Zhe | 2009 | Mol Cancer Res2009，7，5： | 1 |
| 13 | Key cancer cell signal transduction pathways as therapeutic targets显示文摘 | Bianco R Melisi D Ciardiello F | 2006 | Eur J Cancer2006，42，3： | 1 |
| 14 | NF-?cB as a target for pancreaticcancer therapy显示文摘 | Carbone C Melisi D | 2012 | Expert Opin Ther Targets2012，16，2： | 1 |
| 15 | Oral poly(ADP-ribose) polymerase 1 inhibitor BSI-401 has antitumor activity and synergizes with oxaliplatin against pancreatic cancer, preventing acute neurotoxicity显示文摘 | Melisi D Ossovskaya V Zhu C | 2009 | Clin Cancer Res2009，15，20： | 1 |
| 16 | Ly2109761, a novel transforming growth factor beta receptor type I and II dual inhibitor , as a therapeutic approach to sup- pressing pancreatic cancer metastasis 显示文摘 | Melisi D Ishiyama S Sclabas GM | 2008 | Mol Cancer Ther2008，7，4： | 1 |
| 17 | Emerging pathways and future targets for the molecular therapy of pancreatic cancer显示文摘 | Vaccaro V Melisi D Bria E | 2011 | Expert Opin Ther Targets2011，15，10： | 1 |
| 18 | NF-KB as a target for pancreatic cancer therapy 显示文摘 | Carbone C Melisi D | 2012 | Expert Opin Ther Targets2012，16，2： | 1 |
| 19 | Modulation of pancreatic cancer chemoresistance by inhibition of TAK1显示文摘 | Melisi D Xia Q Paradiso G | | 0，，15： | 1 |
| 20 | Modulation of pancreatic cancer chemoresistance by inhibition of TAKI显示文摘 | MELISI D XIA Qianghua PARADISO G | 2011 | J Natl Cancer Inst2011，103，15： | 1 |
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