Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer

Wolpin, Brian M.; Hezel, Aram F.; Abrams, Thomas; Blaszkowsky, Lawrence S.; Meyerhardt, Jeffrey A.; Chan, Jennifer A.; Enzinger, Peter C.; Allen, Brittany; Clark, Jeffrey W.; Ryan, David P.; Fuchs, Charles S.

doi:10.1200/jco.2008.18.9514

Cited by 297Pancreatic and Hepatic Oncology ResearchPI3K/AKT/mTOR signaling in cancerPancreatitis Pathology and Treatment

Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer

Open access

Wolpin, Brian M., Hezel, Aram F., Abrams, Thomas, Blaszkowsky, Lawrence S., Meyerhardt, Jeffrey A., Chan, Jennifer A., Enzinger, Peter C., Allen, Brittany +3 more·2009·Journal of Clinical Oncology

DOI 10.1200/jco.2008.18.9514PMC PMC2645085

Open this paper in CoChat — free account

Abstract

Purpose: The PI3K/Akt/mTOR pathway is activated in the majority of pancreatic cancers, and inhibition of this pathway has antitumor effects in preclinical studies. We performed a multi-institutional, single-arm, phase II study of RAD001(everolimus), an oral inhibitor of mTOR, in patients who experienced treatment failure on first-line therapy with gemcitabine. Patients and Methods: Thirty-three patients with gemcitabine-refractory, metastatic pancreatic cancer were treated continuously with RAD001 at 10 mg daily. Prior treatment with fluorouracil in the perioperative setting was allowed. Patients were observed for toxicity, treatment response, and survival. Results: Treatment with single-agent RAD001 was well-tolerated; the most common adverse events were mild hyperglycemia and thrombocytopenia. No patients were removed from the study because of drug-related adverse events. No complete or partial treatment responses were noted, and only seven patients (21%) had stable disease at the first restaging scans performed at 2 months. Median progression-free survival and overall survival were 1.8 months and 4.5 months, respectively. One patient (3%) had a biochemical response, defined as ≥ 50% reduction in serum CA19-9. Conclusion: Although well-tolerated, RAD001 administered as a single-agent had minimal clinical activity in patients with gemcitabine-refractory, metastatic pancreatic cancer. Future studies in metastatic pancreatic cancer should assess the combination of mTOR inhibitors with other agents and/or examine inhibitors of other components of the PI3K/Akt/mTOR pathway.

Integrity signals

Registry

Crossref · 10.1200/jco.2008.18.9514

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Single-agent phase II trials of the mTOR inhibitors temsirolimus and everolimus demonstrated minimal clinical activity.
“In single agent phase II trials of the mTOR inhibitors temsirolimus and everolimus, very little clinical activity was seen (90, 91).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [91]

1 retracted

RETRACTED: Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade
Shi, Y., Yan, H., Frost, P., Gera, J., & Lichtenstein, A. K. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0068 · Cited by 368 · see citing works
Retracted
Cancer Statistics, 2008
Jemal, A., Siegel, R. L., Ward, E., Hao, Y., Xu, J., Murray, T., & Thun, M. J. (2008) · CA A Cancer Journal for Clinicians · doi:10.3322/ca.2007.0010 · Cited by 10,184 · see citing works
Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.
Burris, H. A., Moore, M. J., Andersen, J., Green, M. R., Rothenberg, M. L., Modiano, M., Cripps, M. C., Portenoy, R. K., Storniolo, A. M., Tarassoff, P. G., et al. (1997) · Journal of Clinical Oncology · doi:10.1200/jco.1997.15.6.2403 · Cited by 5,895 · see citing works
Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group
Moore, M. J., Goldstein, D., Hamm, J., Figer, A., Hecht, J. R., Gallinger, S., Au, H. J., Murawa, P., Walde, D., Wolff, R. A., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.9525 · Cited by 3,848 · see citing works
mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt
O'Reilly, K. E., Rojo, F., She, Q.-B., Solit, D., Mills, G. B., Smith, D., Lane, H., Hofmann, F., Hicklin, D. J., Ludwig, D. L., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2925 · Cited by 2,561 · see citing works
Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes
Almoguera, C., Shibata, D. K., Forrester, K., Wj, M., Arnheim, N., & Perucho, M. (1988) · Cell · doi:10.1016/0092-8674(88)90571-5 · Cited by 2,100 · see citing works
Genetics and biology of pancreatic ductal adenocarcinomaPreprint
Hezel, A. F., Kimmelman, A. C., Stanger, B. Z., Bardeesy, N. M., & DePinho, R. A. (2006) · Genes & Development · doi:10.1101/gad.1415606 · Cited by 1,570 · see citing works
Self-citation
Insulin-like growth factors and neoplasia
Pollak, M., Schernhammer, E. S., & Hankinson, S. E. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1387 · Cited by 1,465 · see citing works
mTOR and cancer: insights into a complex relationship
Sabatini, D. M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1974 · Cited by 1,322 · see citing works
Targeting the PI3K-Akt pathway in human cancer
Luo, J., Manning, B. D., & Cantley, L. C. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00248-4 · Cited by 1,290 · see citing works
Gemcitabine in Combination With Oxaliplatin Compared With Gemcitabine Alone in Locally Advanced or Metastatic Pancreatic Cancer: Results of a GERCOR and GISCAD Phase III Trial
Louvet, C., Labianca, R., Hammel, P. R., Lledo, G., Zampino, M. G., André, T., Zaniboni, A., Ducreux, M. P., Aitini, E., Taı̈eb, J., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.06.023 · Cited by 948 · see citing works
Activation of Akt and eIF4E Survival Pathways by Rapamycin-Mediated Mammalian Target of Rapamycin Inhibition
Sun, S., Rosenberg, L. M., Wang, X., Zhou, Z., Yue, P., Fu, H., & Khuri, F. R. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0917 · Cited by 800 · see citing works
Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA.
Cheng, J. Q., Ruggeri, B., Klein, W. M., Sonoda, G., Altomare, D. A., Watson, D. K., & Testa, J. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3636 · Cited by 793 · see citing works
Phase III Study of Gemcitabine in Combination With Fluorouracil Versus Gemcitabine Alone in Patients With Advanced Pancreatic Carcinoma: Eastern Cooperative Oncology Group Trial E2297
Berlin, J. D., Catalano, P. J., Thomas, J. P., Kugler, J. W., Haller, D. G., & Benson, A. B. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.11.149 · Cited by 728 · see citing works
Physical Activity, Obesity, Height, and the Risk of Pancreatic Cancer
Michaud, D. S. (2001) · JAMA · doi:10.1001/jama.286.8.921 · Cited by 663 · see citing works
Gemcitabine Plus Capecitabine Compared With Gemcitabine Alone in Advanced Pancreatic Cancer: A Randomized, Multicenter, Phase III Trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group
Herrmann, R., Bodoky, G., Ruhstaller, T., Glimelius, B. L. G., Bajetta, E., Schueller, J., Saletti, P., Bauer, J. A., Figer, A., Pestalozzi, B. C., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.09.0886 · Cited by 594 · see citing works
Irinotecan Plus Gemcitabine Results in No Survival Advantage Compared With Gemcitabine Monotherapy in Patients With Locally Advanced or Metastatic Pancreatic Cancer Despite Increased Tumor Response Rate
Lima, C. M. R., Green, M. R., Rotche, R., Miller, W. H., Jeffrey, G. M., Cisar, L. A., Morganti, A., Orlando, N., Gruia, G., & Miller, L. L. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.12.082 · Cited by 587 · see citing works
Oncogenic Mutations of PIK3CA in Human Cancers
Samuels, Y., & Velculescu, V. E. (2004) · Cell Cycle · doi:10.4161/cc.3.10.1164 · Cited by 539 · see citing works
Dose- and Schedule-Dependent Inhibition of the Mammalian Target of Rapamycin Pathway With Everolimus: A Phase I Tumor Pharmacodynamic Study in Patients With Advanced Solid Tumors
Tabernero, J. M., Rojo, F., Calvo, E., Burris, H. A., Judson, I. R., Hazell, K., Martinelli, E., y Cajal, S. R., Jones, S. F., Vidal, L., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.5482 · Cited by 537 · see citing works
Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral Mammalian Target of Rapamycin Inhibitor Everolimus in Patients With Advanced Solid Tumors
O’Donnell, A. E., Faivre, S. J., Burris, H. A., Rea, D. W., Papadimitrakopoulou, V. A., Shand, N., Lane, H. A., Hazell, K., Zoellner, U., Kovarik, J. M., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.0988 · Cited by 478 · see citing works
p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma.
Moskaluk, C. A., Hruban, R. H., & Kern, S. E. (1997) · PubMed · Cited by 429 · see citing works
Insulin, Glucose, Insulin Resistance, and Pancreatic Cancer in Male Smokers
Stolzenberg‐Solomon, R. Z. (2005) · JAMA · doi:10.1001/jama.294.22.2872 · Cited by 400 · see citing works
Upstream of the mammalian target of rapamycin: do all roads pass through mTOR?
Corradetti, M. N., & Guan, K.-L. (2006) · Oncogene · doi:10.1038/sj.onc.1209885 · Cited by 387 · see citing works
Stress and mTORture signaling
Reiling, J. H., & Sabatini, D. M. (2006) · Oncogene · doi:10.1038/sj.onc.1209889 · Cited by 338 · see citing works
The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-κB and c-Myc in pancreatic cancer cells
Asano, T., Yao, Y., Zhu, J., Li, D., Abbruzzese, J. L., & Reddy, S. A. G. (2004) · Oncogene · doi:10.1038/sj.onc.1207902 · Cited by 303 · see citing works
Incidence, mechanism and prognostic value of activated AKT in pancreas cancer
Schlieman, M. G., Fahy, B. N., Ramsamooj, R., et al. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601396 · Cited by 261 · see citing works
Prognostic Significance of Activated Akt Expression in Pancreatic Ductal Adenocarcinoma
Yamamoto, S., Tomita, Y., Hoshida, Y., Morooka, T., Nagano, H., Dono, K., Umeshita, K., Sakon, M., Ishikawa, O., Ohigashi, H., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-02-1441 · Cited by 241 · see citing works
A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis of Cancer and Leukemia Group B (CALGB
Kindler, H. L., Niedzwiecki, D., Hollis, D. R., Oraefo, E., Schrag, D., Hurwitz, H. I., McLeod, H. L., Mulcahy, M. F., Schilsky, R. L., & Goldberg, R. M. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.25.18_suppl.4508 · Cited by 235 · see citing works
Inhibition of the phosphatidylinositol 3'-kinase-AKT pathway induces apoptosis in pancreatic carcinoma cells in vitro and in vivo.
Bondar, V. M., Sweeney‐Gotsch, B., Andreeff, M., Mills, G. B., & McConkey, D. J. (2002) · PubMed · Cited by 234 · see citing works
Identifying Optimal Biologic Doses of Everolimus (RAD001) in Patients With Cancer Based on the Modeling of Preclinical and Clinical Pharmacokinetic and Pharmacodynamic Data
Tanaka, C., O’Reilly, T., Kovarik, J. M., Shand, N., Hazell, K., Judson, I. R., Raymond, É., Zumstein-Mecker, S., Stephan, C., Boulay, A., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.1127 · Cited by 211 · see citing works
Phase III study of gemcitabine [G] plus cetuximab [C] versus gemcitabine in patients [pts] with locally advanced or metastatic pancreatic adenocarcinoma [PC]: SWOG S0205 study
Philip, P. A., Benedetti, J., Fenoglio‐Preiser, C. M., Zalupski, M. M., Lenz, H., O'Reilly, E. M., Wong, R., Atkins, J., Abruzzese, J. L., & Blanke, C. D. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.25.18_suppl.lba4509 · Cited by 185 · see citing works
Frequent activation of AKT2 kinase in human pancreatic carcinomas
Altomare, D. A., Tanno, S., Rienzo, A. D., Klein–Szanto, A. J., Tanno, S., Skele, K. L., Hoffman, J. P., & Testa, J. R. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10287 · Cited by 174 · see citing works
Capecitabine Plus Erlotinib in Gemcitabine-Refractory Advanced Pancreatic Cancer
Kulke, M. H., Blaszkowsky, L. S., Ryan, D. P., Clark, J. W., Meyerhardt, J. A., Zhu, A. X., Enzinger, P. C., Kwak, E. L., Muzikansky, A., Lawrence, C. E., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.11.8521 · Cited by 164 · see citing works
Self-citation
Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study
Demols, A., Peeters, M., Polus, M., Maréchal, R., Gay, F., Monsaert, E., Hendlisz, A., & Laethem, J. V. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6602966 · Cited by 138 · see citing works
Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma
Ulrich-Pur, H., Raderer, M., Kornek, G. V., Schüll, B., Schmid, K., Haider, K., Kwasny, W., Depisch, D., Schneeweiß, B., Lang, F., et al. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6600883 · Cited by 117 · see citing works
In vivo antitumor effect of the mTOR inhibitor CCI‐779 and gemcitabine in xenograft models of human pancreatic cancer
Ito, D., Fujimoto, K., Mori, T., Kami, K., Koizumi, M., Toyoda, E., Kawaguchi, Y., & Doi, R. (2005) · International Journal of Cancer · doi:10.1002/ijc.21532 · Cited by 117 · see citing works
Rapamycin-Induced Endothelial Cell Death and Tumor Vessel Thrombosis Potentiate Cytotoxic Therapy against Pancreatic Cancer
Bruns, C. J., Koehl, G. E., Guba, M. O., Yezhelyev, M., Steinbauer, M. G. M., Seeliger, H., Schwend, A., Hoehn, A., Jauch, K., & Geissler, E. K. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0502 · Cited by 115 · see citing works
Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: A phase II study
Tsavaris, N. B., Kosmas, C., Skopelitis, H., et al. (2005) · Investigational New Drugs · doi:10.1007/s10637-005-1446-y · Cited by 105 · see citing works
Pancreatic Cancer Cell Proliferation Is Phosphatidylinositol 3-Kinase Dependent
Perugini, R. A., McDade, T. P., Vittimberga, F. J., & Callery, M. P. (2000) · Journal of Surgical Research · doi:10.1006/jsre.2000.5833 · Cited by 100 · see citing works
Paclitaxel as weekly second-line therapy in patients with advanced pancreatic carcinoma
Oettle, H., Arnold, D., Esser, M., et al. (2000) · Anti-Cancer Drugs · doi:10.1097/00001813-200009000-00006 · Cited by 93 · see citing works
Combined Irinotecan and Oxaliplatin in Patients with Advanced Pre-Treated Pancreatic Cancer
Cantore, M., Rabbi, C., Fiorentini, G., Oliani, C., Zamagni, D., Iacono, C., Mambrini, A., Freo, A. D., & Manni, A. (2004) · Oncology · doi:10.1159/000080993 · Cited by 77 · see citing works
The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation.
Asano, T., Yao, Y.-X., Zhu, J.-J., Li, D.-H., Abbruzzese, J., & Reddy, S. A. (2005) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2005.03.166 · Cited by 74 · see citing works
Raltitrexed–eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer
Reni, M., Pasetto, L. M., Aprile, G., et al. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603026 · Cited by 71 · see citing works
Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial
Boeck, S. H., Weigang-Köhler, K., Fuchs, M., Kettner, E., Quietzsch, D., Trojan, J., Stötzer, O. J., Zeuzem, S., Lordick, F., Köhne, C.-H., et al. (2007) · Annals of Oncology · doi:10.1093/annonc/mdl463 · Cited by 68 · see citing works
A new mouse model of pancreatic cancer: PTEN gets its Akt together
Maitra, A., & Hruban, R. H. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.08.007 · Cited by 31 · see citing works
Second-Line Therapy in Gemcitabine-Pretreated Patients With Advanced Pancreatic Cancer
Boeck, S. H., & Heinemann, V. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.3304 · Cited by 24 · see citing works
The PI3-K/AKT/mTOR pathway as a target for breast cancer therapy
Cosimo, S. D., Scaltriti, M., del Val, D. J., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.25.18_suppl.3511 · Cited by 22 · see citing works
Laparoscopic radiofrequency ablation and systemic chemotherapy for colorectal liver metastases
McCain, D. A. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.22.14_suppl.3776 · Cited by 13 · see citing works

Flagged first, then by citations

Sorted by citations

The mTOR Signalling Pathway in Human Cancer
Pópulo, H., Lopes, J. M., & Soares, P. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13021886 · Cited by 830 · see citing works
KRAS mutation in pancreatic cancer
Luo, J. (2021) · Seminars in Oncology · doi:10.1053/j.seminoncol.2021.02.003 · Cited by 360 · see citing works
A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy
Bodoky, G., Timcheva, C., Spigel, D. R., La Stella, P. J., Ciuleanu, T. E., Pover, G., & Tebbutt, N. C. (2012) · Investigational New Drugs · doi:10.1007/s10637-011-9687-4 · Cited by 236 · see citing works
Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies
Javle, M. M., Shroff, R. T., Xiong, H., Varadhachary, G. A., Fogelman, D., Reddy, S. A., Davis, D., Zhang, Y., Wolff, R. A., & Abbruzzese, J. L. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-368 · Cited by 170 · see citing works
Mutations in key driver genes of pancreatic cancer: molecularly targeted therapies and other clinical implications
Hu, H.-F., Ye, Z., Qin, Y., Xu, X.-W., Yu, X.-J., Zhuo, Q.-F., & Ji, S.-R. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00584-2 · Cited by 149 · see citing works
Phase II study of capecitabine and the oral mTOR inhibitor everolimus in patients with advanced pancreatic cancer
Kordes, S., Klümpen, H. J., Weterman, M. J., Schellens, J. H. M., Richel, D. J., & Wilmink, J. W. (2015) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-015-2730-y · Cited by 71 · see citing works
Anti-tumor Effects of Everolimus and Metformin Are Complementary and Glucose-dependent in Breast Cancer Cells
Ariaans, G., Jalving, M., Vries, E. G. E. D., & Jong, S. D. (2017) · BMC Cancer · doi:10.1186/s12885-017-3230-8 · Cited by 51 · see citing works
Insulin-Like Growth Factor Signaling as a Therapeutic Target in Pancreatic Cancer
Rieder, S., W. Michalski, C., Friess, H., & Kleeff, >. (2011) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/187152011795677454 · Cited by 50 · see citing works
<i>KRAS</i> Mutation Variants and Co-occurring PI3K Pathway Alterations Impact Survival for Patients with Pancreatic Ductal Adenocarcinomas
Diehl, A. C., Hannan, L. M., Zhen, D. B., Coveler, A. L., King, G., Cohen, S. A., Harris, W. P., Shankaran, V., Wong, K. M., Green, S., et al. (2022) · The Oncologist · doi:10.1093/oncolo/oyac179 · Cited by 35 · see citing works
Gemcitabine combined with the mTOR inhibitor temsirolimus in patients with locally advanced or metastatic pancreatic cancer. a hellenic cooperative oncology group phase I/II study
Karavasilis, V., Samantas, E., Koliou, G.-A., Kalogera-Fountzila, A., Pentheroudakis, G., Varthalitis, I., Linardou, H., Rallis, G., Skondra, M., Papadopoulos, G., et al. (2018) · Targeted Oncology · doi:10.1007/s11523-018-0605-y · Cited by 27 · see citing works

Gemcitabine Resistance is Associated with Epithelial-Mesenchymal Transition and Induction of HIF-1&#945; in Pancreatic Cancer Cells
Wang, R., Cheng, L., Xia, J., Wang, Z., Wu, Q., & Wang, Z. (2014) · Current Cancer Drug Targets · doi:10.2174/1568009614666140226114015 · Cited by 56 · see citing works
Selenium Induces Pancreatic Cancer Cell Death Alone and in Combination with Gemcitabine
Wooten, D. J., Sinha, I., & Sinha, R. (2022) · Biomedicines · doi:10.3390/biomedicines10010149 · Cited by 11 · see citing works
Aberrant expression of circulating microRNAs in pancreatic cancer patients and in patients with gemcitabine resistance
Wang, S., Zhou, F., & Wang, L. (2014) · 国际外科学杂志 · doi:10.3760/cma.j.issn.1673-4203.2014.05.014
Natural Anti-Cancer Agents: Implications in Gemcitabine-Resistant Pancreatic Cancer Treatment
Marasini, B., & Sahu, R. P. (2017) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557517666170315124438 · Cited by 28 · see citing works
USP9X inhibition improves gemcitabine sensitivity in pancreatic cancer by inhibiting autophagy
Ma, T., Chen, W., Zhi, X., et al. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.08.010 · Cited by 69 · see citing works

Authors: Wolpin, B. M., Hezel, A. F., Abrams, T., Blaszkowsky, L. S., Meyerhardt, J. A., Chan, J. A., Enzinger, P. C., Allen, B., Clark, J. W., Ryan, D. P., & Fuchs, C. S.
Affiliations: Brigham and Women's Hospital (US)
ORCID: Wolpin, Brian M.
Hezel, Aram F.
Abrams, Thomas
Blaszkowsky, Lawrence S.
Meyerhardt, Jeffrey A.
Chan, Jennifer A.
Enzinger, Peter C.
Allen, Brittany
Clark, Jeffrey W.
Ryan, David P.
Fuchs, Charles S.
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2009-01-10
Volume: 27
Issue: 2
Pages: 193-198
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2008.18.9514
PMC: PMC2645085
OpenAlex: W2154108823
Cited by: 297
References: 48
Citations by year: 2026: 4 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 19 · 2021: 14 · 2020: 15 · 2019: 13 · 2018: 13 · 2017: 21 · 2016: 14 · 2015: 34 · 2014: 24 · 2013: 17 · 2012: 26
FWCI: 10.75
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Clinical Oncology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (P50CA127003, T32 CA09001, P01 CA 55075, P01CA087969, P01CA055075, P01 CA124908, [P01 CA87969, T32CA009001)
Topics: Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
Keywords: everolimus, mTOR inhibitors, metastatic pancreatic cancer, gemcitabine-refractory disease, PI3K/AKT/mTOR pathway, monotherapy, treatment toxicity, progression-free survival, CA19-9 response, hyperglycemia, thrombocytopenia
MeSH terms: Everolimus, Phosphoinositide-3 Kinase Inhibitors, Gemcitabine, Administration, Oral, Adult, Aged, Deoxycytidine, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, Protein Kinases, Signal Transduction, Drug Resistance, Neoplasm, Phosphatidylinositol 3-Kinases, Sirolimus, Oncogene Protein v-akt, TOR Serine-Threonine Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks