Results from a Phase 2 Study of Ruxolitinib or Placebo with Capecitabine as Second-Line Therapy in Patients with Metastatic Pancreatic Cancer: The Recap Trial

Hurwitz, H.; Uppal, Nikhil; Wagner, Stéphanie; Bendell, J. C.; Thaddeus, B.J.; Wade, Seaborn Mcdonald; Nemunaitis, John; Stella, Philip J.; Pipas, J. Marc; Wainberg, Zev A.; Manges, Robert; Garrett, William M.; Hunter, Deborah; Clark, Jason; Leopold, Lance; Levy, Richard S.; Sandor, Victor

doi:10.1093/annonc/mdu193.26

Cited by 4 publications

(5 citation statements)

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“…Although it was found to reduce JAK2 activation in these cells, increased phosphorylation of Bcr-Abl was observed, suggesting that a compensatory mechanism may be simultaneously activated. Another JAK1/2 inhibitor, ruxolitinib, has been approved for the treatment of myelofibrosis but is associated with adverse effects, including thrombocytopenia and anemia (39,87). Ruxolitinib has been shown to have anticancer effects in cisplatin-resistant non-small cell lung cancer and pancreatic cancer cell lines by inducing apoptosis and blocking STAT3 activation (35,39).…”

Section: Pharmacological Inhibition Of Stat3mentioning

confidence: 99%

“…Another JAK1/2 inhibitor, ruxolitinib, has been approved for the treatment of myelofibrosis but is associated with adverse effects, including thrombocytopenia and anemia (39,87). Ruxolitinib has been shown to have anticancer effects in cisplatin-resistant non-small cell lung cancer and pancreatic cancer cell lines by inducing apoptosis and blocking STAT3 activation (35,39). A randomized phase II clinical trial examining the effects of JAK1/2 inhibitor baricitinib in the progression of diabetic kidney disease (DKD) was recently completed (NCT01683409).…”

Section: Pharmacological Inhibition Of Stat3mentioning

confidence: 99%

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Targeting STAT3 signaling in kidney disease

Pace

Paladugu

Das

et al. 2019

American Journal of Physiology-Renal Physiology

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The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a multifaceted transduction system that regulates cellular responses to incoming signaling ligands. STAT3 is a central member of the JAK/STAT signaling cascade and has long been recognized for its increased transcriptional activity in cancers and autoimmune disorders but has only recently been in the spotlight for its role in the progression of kidney disease. Although genetic knockout and manipulation studies have demonstrated the salutary benefits of inhibiting STAT3 activity in several kidney disease models, pharmacological inhibition has yet to make it to the clinical forefront. In recent years, significant effort has been aimed at suppressing STAT3 activation for treatment of cancers, which has led to the development of a wide variety of STAT3 inhibitors, but only a handful have been tested in kidney disease models. Here, we review the detrimental role of dysregulated STAT3 activation in a variety of kidney diseases and the current progress in the treatment of kidney diseases with pharmacological inhibition of STAT3 activity.

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Section: Pharmacological Inhibition Of Stat3mentioning

confidence: 99%

Section: Pharmacological Inhibition Of Stat3mentioning

confidence: 99%

Targeting STAT3 signaling in kidney disease

Pace

Paladugu

Das

et al. 2019

American Journal of Physiology-Renal Physiology

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show abstract

“…With respect to gastrointestinal malignancies, ruxolitinib, a JAK1 and JAK2 inhibitor, has demonstrated preliminary efficacy in combination with capecitabine in pancreatic adenocarcinoma and is currently under evaluation in colorectal cancer in combination with regorafenib [ClinicalTrials.gov identifier: NCI02119676] [Hurwitz et al 2014]. To our knowledge there are no trials ongoing in GC.…”

Section: Molecular Characterization From the Tcga Analysismentioning

confidence: 99%

Novel targets in the treatment of advanced gastric cancer: a perspective review

Fontana

Smyth

2016

Ther Adv Med Oncol

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Gastric cancer is responsible for a high burden of disease globally. Although more extensive use of chemotherapy together with the recent introduction of the two targeted agents trastuzumab and ramucirumab have contributed to marginal outcome prolongation, overall survival for patients with advanced stage disease remains poor. Over the last decade, a number of novel agents have been examined in clinical trials with largely disappointing results. Potential explanations for this are the absence of molecularly selected trial populations or weak predictive biomarkers within the context of a highly heterogeneous disease. In the recently published gastric cancer The Cancer Genome Atlas (TCGA) project a new classification of four different tumour subtypes according to different molecular characteristics has been proposed. With some overlap, several relatively distinct and potentially targetable pathways have been identified for each subtype. In this perspective review we match recent trial results with the subtypes described in the gastric cancer TCGA aiming to highlight data regarding novel agents under evaluation and to discuss whether this publication might provide a framework for future drug development.

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“…The results were recently presented at the ESMO 16th World Congress on Gastrointestinal Cancer. In the overall patient population, there was no statistically significant difference on OS (HR: 0.79; 95% CI: 0.53-1.18) [59]. However, in a preplanned subgroup analysis; patients with higher markers of inflammation demonstrated statistically significant 3-and 6-month REviEW Kundranda & Kachaamy future science group survival in the ruxolitinib arm.…”

Section: Jak-stat Pathwaymentioning

confidence: 89%

Promising New Therapies in Advanced Pancreatic Adenocarcinomas

Kundranda

Kachaamy

2014

Future Oncol.

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Pancreatic ductal adenocarcinoma is a lethal disease due to late diagnosis, early metastasis and the lack of effective therapies. In patients with metastatic disease, 1-year survival ranges from 17 to 23% and 5-year survival is less than 5%. This necessitates an urgent need for developing more effective therapies. Targeting the neoplastic cells has been largely ineffective due to the dense stroma, which is a physical barrier for effective drug delivery and also a source for different factors that promote tumor progression and immunosuppression. In this review, we focus on understanding the complex biology of this tumor as it relates to the evaluation of previously failed molecularly targeted trials and review potential new therapies that are emerging in the treatment of metastatic pancreatic ductal adenocarcinoma.

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Results from a Phase 2 Study of Ruxolitinib or Placebo with Capecitabine as Second-Line Therapy in Patients with Metastatic Pancreatic Cancer: The Recap Trial

Cited by 4 publications

References 0 publications

Targeting STAT3 signaling in kidney disease

Targeting STAT3 signaling in kidney disease

Novel targets in the treatment of advanced gastric cancer: a perspective review

Promising New Therapies in Advanced Pancreatic Adenocarcinomas

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