Second-line therapy for advanced pancreatic cancer: A review of the literature and future directions

Custodio, Ana; Puente, Javier; Sastre, Javier; Dı́az-Rubio, Eduardo

doi:10.1016/j.ctrv.2009.08.012

Cited by 29 publications

(22 citation statements)

References 66 publications

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“…Moreover, a number of apoptosis markers, as well as the ability of these agents to induce apoptosis, was also investigated. We also examined the anti-proliferative activity of DFO, Dp44mT and DpC against four different pancreatic cancer cell types in vitro compared with the standard chemotherapeutics for this disease, namely gemcitabine and 5-fluorouracil (Custodio et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

“…Although there have been increasing efforts to better understand the pathogenesis and improve treatment options for pancreatic cancer (Custodio et al, 2009;Furukawa, 2009), the prognosis for those with this illness remains poor. The standard treatment for pancreatic cancer is the anticancer agent gemcitabine (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Gemcitabine is an analog of the nucleoside deoxycytidine, which functions to inhibit ribonucleotide reductase and also initiates DNA strand termination and apoptosis (Wong et al, 2009). However, the success of gemcitabine and its combinations with other agents for pancreatic cancer treatment has been limited, with an average increase in patient lifespan of only 3 months (Custodio et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…1A), often given in combination with other chemotherapeutics such as 5-fluorouracil (Fig. 1B) (Custodio et al, 2009). Gemcitabine is an analog of the nucleoside deoxycytidine, which functions to inhibit ribonucleotide reductase and also initiates DNA strand termination and apoptosis (Wong et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Novel Thiosemicarbazone Iron Chelators Induce Up-Regulation and Phosphorylation of the Metastasis Suppressor N-myc Down-Stream Regulated Gene 1: A New Strategy for the Treatment of Pancreatic Cancer

Kovačević

Chikhani

Lovejoy

et al. 2011

Molecular Pharmacology

159

261

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Pancreatic cancer is an aggressive neoplasm, with a mortality rate close to 100%. The most successful agent for pancreatic cancer treatment is gemcitabine, although the overall effect in terms of patient survival remains very poor. This study was initiated to evaluate a novel class of anticancer agents against pancreatic cancer. This group of compounds belongs to the dipyridyl thiosemicarbazone class that have been shown to have potent and selective activity against a range of different neoplasms in vitro and in vivo. We demonstrate for the first time in pancreatic cancer that these agents increase the expression of the growth and metastasis suppressor N-myc downstreamregulated gene 1 and its phosphorylation at Ser330 and Thr346 that is important for its activity against this tumor. In addition, these agents increased expression of the cyclin-dependent kinase inhibitor p21 CIP1/WAF1 , whereas decreasing cyclin D1 in pancreatic cancer cells. Together, these molecular alterations account, in part, for the pronounced antitumor activity observed. Indeed, these agents had significantly higher antiproliferative activity in vitro than the established treatments for pancreatic cancer, namely gemcitabine and 5-fluorouracil. Studies in vivo demonstrated that a novel thiosemicarbazone, namely di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone hydrochloride, completely inhibited the growth of pancreatic cancer xenografts with no evidence of marked alterations in normal tissue histology. Together, our studies have identified molecular effectors of a novel and potent antitumor agent that could be useful for pancreatic cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Novel Thiosemicarbazone Iron Chelators Induce Up-Regulation and Phosphorylation of the Metastasis Suppressor N-myc Down-Stream Regulated Gene 1: A New Strategy for the Treatment of Pancreatic Cancer

Kovačević

Chikhani

Lovejoy

et al. 2011

Molecular Pharmacology

159

261

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“…Less data are available for chemo-refractory PC. Second line therapies have been investigated in Phase II trials with limited success [17][18][19][20][21], and there is currently no standard regimen for these patients.…”

Section: Introductionmentioning

confidence: 99%

Phase I trials in patients with relapsed, advanced upper gastrointestinal carcinomas: experience in a specialist unit

Khan¹,

Ang²,

Starling³

et al. 2014

Gastric Cancer

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achieved RECIST-objective response (11 %) with a 6-month clinical benefit rate of 14 %. Median progression free and overall survival were 7.7 weeks [95 %CI 7.7 (6.4-9.0)] and 19.1 weeks (95 %CI 17.5-20.8), respectively. Grade 3 or 4 toxicities were observed in 37 patients (39 %) and led to trial discontinuation in 9 (9 %); no toxicity-related death was recorded. In the multivariate analysis, serum albumin (\35 g/dl, HR2.0, p = 0.002) and lactate dehydrogenase ([192 lmol/l, HR1.7, p = 0.016) were prognostic of overall survival. Conclusion Phase I clinical trials can be considered a reasonable option in selected patients with relapsed UGIC. The use of objective prognosticators may improve selection and risk/benefit profile of patients.

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Pharmacologic and radiotherapeutic interventions for advanced pancreatic cancer

Nagrial

Chantrill

Chin

et al. 2013

Cochrane Database of Systematic Reviews

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Second-line therapy for advanced pancreatic cancer: A review of the literature and future directions

Cited by 29 publications

References 66 publications

Novel Thiosemicarbazone Iron Chelators Induce Up-Regulation and Phosphorylation of the Metastasis Suppressor N-myc Down-Stream Regulated Gene 1: A New Strategy for the Treatment of Pancreatic Cancer

Novel Thiosemicarbazone Iron Chelators Induce Up-Regulation and Phosphorylation of the Metastasis Suppressor N-myc Down-Stream Regulated Gene 1: A New Strategy for the Treatment of Pancreatic Cancer

Phase I trials in patients with relapsed, advanced upper gastrointestinal carcinomas: experience in a specialist unit

Pharmacologic and radiotherapeutic interventions for advanced pancreatic cancer

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