Pancreatic Cancer hENT1 Expression and Survival From Gemcitabine in Patients From the ESPAC-3 Trial

Greenhalf, William; Ghaneh, Paula; Neoptolemos, John P.; Palmer, Daniel H.; Cox, Trevor F.; Lamb, Richard F.; Garner, Elizabeth O.; Campbell, Fiona; Mackey, John R.; Costello, Eithne; Moore, Malcolm J.; Valle, Juan W; McDonald, A. C.; Carter, Ross; Tebbutt, Niall C.; Goldstein, David; Shannon, Jennifer; Dervenis, Christos; Glimelius, Bengt; Deakin, Mark; Charnley, Richard; Lacaine, F; Scarfe, Andrew; Middleton, Mark R.; Anthoney, Alan; Halloran, Christopher; Mayerle, Julia; Oláh, Attila; Jackson, Richard; Rawcliffe, Charlotte; Scarpa, Aldo; Bassi, Claudio; Büchler, Markus W.

doi:10.1093/jnci/djt347

Cited by 245 publications

(214 citation statements)

References 34 publications

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“…Human equilibrative nucleoside transporter 1, which regulates the intracellular uptake of gemcitabine into cancer cells, is a well-established molecular marker that is able to predict susceptibility to gemcitabine or prognosis in patients with pancreatic cancer following treatment (6,20,21). Other molecular markers, including serum tumor markers carcinoembryonic antigen and CA 19-9, tumor tissue Notch 3 mRNA expression levels, and serum interleukin (IL)-6 and IL-1β levels, have been proposed as good markers to predict response to gemcitabinen in PDAC patients (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

“…However, gemcitabine remains a key chemotherapeutic agent for palliative chemotherapy in patients with PDAC due to its moderate anti-tumor effect and limited adverse events. Numerous studies aiming to stratify patients using molecular markers, including human equilibrative nucleoside transporter 1 and ribonucleotide reductase regulatory subunit M1, have been conducted to determine candidates for whom gemcitabine treatment would be optimal (6)(7)(8). These molecular markers are reliable predictive markers for gemcitabine response in patients with PDAC, but typically require specialized equipment that is difficult to utilize in routine clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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Derived neutrophil/lymphocyte ratio predicts gemcitabine therapy outcome in unresectable pancreatic cancer

et al. 2016

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Abstract.As gemcitabine is a key anti-tumor agent for unresectable pancreatic ductal adenocarcinoma (PDAC), it is important to predict the outcomes of gemcitabine chemotherapy. The present study aimed to confirm whether the derived neutrophil-to-lymphocyte ratio (dNLR) is able to predict chemotherapy outcomes. To elucidate the role of dNLR in patients that underwent chemotherapy, the current study evaluated clinicopathological variables in 31 patients with unresectable PDAC treated with gemcitabine. The correlation between clinicopathological variables, and progression-free survival (PFS) and overall survival (OS) time were investigated. Univariate analysis revealed that there were no significant differences in PFS and OS as a function of age (<65 vs. ≥65 years), gender, tumor location (pancreas head vs. body/tail), tumor diameter (<23 vs. ≥23 mm) or serum carbohydrate antigen 19-9 concentration level (<3,800 vs. ≥3,800 U/ml). However, disease stage (locally advanced vs. metastatic) and the dNLR (<2.5 vs. ≥2.5) significantly affected PFS and OS. Multivariate analysis subsequently revealed that a dNLR of ≥2.5 was an independent prognostic factor for poor PFS (P=0.003) and OS (P=0.026). In conclusion, data from the present study suggests that the pre-treatment dNLR is an independent prognostic factor to predict PFS and OS in patients with unresectable PDAC treated with gemcitabine. This indicates that dNLR has a potential role in stratifying patients that may benefit from gemcitabine therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Derived neutrophil/lymphocyte ratio predicts gemcitabine therapy outcome in unresectable pancreatic cancer

et al. 2016

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“…117,168 Therefore, reduced expression of nucleoside transporters on tumor cells causes tumor cell resistance to gemcitabine. 123,169 For example, it was reported that high hENT1 expression in resected specimen of patients with PDAC who received postoperative gemcitabine therapy is correlated with increased overall survival, [170][171][172][173] whereas low hENT1 expression was linked to gemcitabine resistance and shorter overall survival. 109,123,169 In addition, low levels of hENT1 expression were also detected in tumors in gallbladder adenocarcinoma patients who respond poorly to gemcitabine.…”

Section: Increasing Cellular Uptake Of Gemcitabinementioning

confidence: 99%

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Chen¹,

Zheng²,

Shi³

et al. 2018

IJN

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Despite recent advances in targeted therapies and immunotherapies, chemotherapy using cytotoxic agents remains an indispensable modality in cancer treatment. Recently, there has been a growing emphasis in using nanomedicine in cancer chemotherapy, and several nanomedicines have already been used clinically to treat cancers. There is evidence that formulating small molecular cancer chemotherapeutic agents into nanomedicines significantly modifies their pharmacokinetics and often improves their efficacy. Importantly, cancer cells often develop resistance to chemotherapy, and formulating anticancer drugs into nanomedicines also helps overcome chemoresistance. In this review, we briefly describe the different classes of cancer chemotherapeutic agents, their mechanisms of action and resistance, and evidence of overcoming the resistance using nanomedicines. We then emphasize on gemcitabine and our experience in discovering the unique (stearoyl) gemcitabine solid lipid nanoparticles that are effective against tumor cells resistant to gemcitabine and elucidate the underlying mechanisms. It seems that lysosomes, which are an obstacle in the delivery of many drugs, are actually beneficial for our (stearoyl) gemcitabine solid lipid nanoparticles to overcome tumor cell resistance to gemcitabine.

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“…Экспрессия hENT1, определяемая иммуногистохимически в опухоли с помощью антитела 10D7G2, оказалась пре-диктором повышенной эффективно-сти гемцитабина у пациентов, полу-чавших гемцитабин в адъювантном режиме в исследованиях ESPAC-3 и RTOG 9704 [54,55]. Предиктив ная роль hENT1 не была подтверждена при использовании другого антитела SP120 [56][57][58].…”

Section: возможности индивидуализации терапии рака поджелудочной железыunclassified

Combination Chemotherapy Regimens in Pancreatic Cancer

Попова¹,

Pokataev²,

Тюляндин³

2017

Med. sov.

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Рак поджелудочной железы характеризуется агрессивным течением и высоким метастатическим потенциалом, в связи с чем в большинстве случаев заболевание выявляется на неоперабельных стадиях. Основным методом лечения местнораспро-страненного и метастатического рака поджелудочной железы является химиотерапия. До недавнего времени стандартом химиотерапии данной патологии считалась монотерапия гемцитабином, пока в клиническую практику не вошли более эффективные режимы комбинированной химиотерапии (FOLFIRINOX и комбинация nab-паклитаксела с гемцитабином). Назначение данных схем химиотерапии лимитирует относительно высокая токсичность, что делает невозможным их при-менение у ослабленных пациентов и у больных с серьезной сопутствующей патологией. В настоящей работе рассматривают-ся критерии выбора оптимального режима комбинированной химиотерапии на основе оценки состояния пациента, возмож-ности управления побочными эффектами химиотерапии, а также молекулярно-биологические характеристики опухоли.

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Pancreatic Cancer hENT1 Expression and Survival From Gemcitabine in Patients From the ESPAC-3 Trial

Abstract: Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

Cited by 245 publications

References 34 publications

Derived neutrophil/lymphocyte ratio predicts gemcitabine therapy outcome in unresectable pancreatic cancer

Derived neutrophil/lymphocyte ratio predicts gemcitabine therapy outcome in unresectable pancreatic cancer

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Combination Chemotherapy Regimens in Pancreatic Cancer

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