Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis?

Mizuguchi, Toru; Torigoe, Toshihiko; Satomi, Fukino; Shima, Hiroaki; Kutomi, Goro; Ota, Shinichiro; Imamura, Masayuki; Hayashi, Hiroshi; Asakura, Sumiyo; Hirohashi, Yoshihiko; Meguro, Makoto; Kimura, Yasutoshi; Nishidate, Toshihiko; Okita, Kenji; Ishino, Masaho; Miyamoto, Atsushi; Hatakenaka, Masamitsu; Sato, Noriyuki; Hirata, Koichi

doi:10.1007/s00595-015-1120-8

Cited by 14 publications

(9 citation statements)

References 60 publications

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“…Pancreatic ductal adenocarcinoma (PDAC), a lethal neoplasm with a 5-year survival rate of approximately 5%, is increasing worldwide 1 2 3 4 . Several challenges must be overcome to improve the prognosis of this devastating malignancy: a lack of early detection because of the propensity for early local invasion or distant metastasis; limited treatment options; and an insufficient understanding of PDAC biology.…”

mentioning

confidence: 99%

MicroRNA-155 Controls Exosome Synthesis and Promotes Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma

Mikamori

Yamada

Eguchi

et al. 2017

Sci Rep

219

161

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The cancer drug gemcitabine (GEM) is a key drug for treating pancreatic ductal adenocarcinoma (PDAC), but PDAC cells develop chemoresistance after long-term administration. Since the tolerance was immediately spread to every PDAC tissue in a patient, it is assumed that some certain efficient mechanisms underlay in the development of chemoresistance. Changes in the levels of particular microRNAs or alterations in intercellular communication play a dominant role in chemoresistance development, and recent data also suggest that exosomes play an important role in this process. In this study, we revealed that the loop conferred chemoresistance in PDAC cells. The loop was as follows; 1, The long-term exposure of GEM increased miR-155 expression in PDAC cells. 2, The increase of miR-155 induced two different functions; exosome secretion and chemoresistance ability via facilitating the anti-apoptotic activity. 3, Exosome deliver the miR-155 into the other PDAC cells and induce the following function. The target therapy to miR-155 or the exosome secretion effectively attenuated the chemoresistance, and these results were validated with both clinical samples and in vivo experiments. This mechanism represents a novel therapeutic target in GEM treatment to PDAC.

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mentioning

confidence: 99%

MicroRNA-155 Controls Exosome Synthesis and Promotes Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma

Mikamori

Yamada

Eguchi

et al. 2017

Sci Rep

219

161

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show abstract

“…There are high expectations concerning utilisation of vaccines in cancer therapy to enhance the natural response of the immune system. Unfortunately, from 19 studies only three demonstrated a complete response, and each counted a small number of patients [ 77 ]. Despite such discouraging results, vaccines remain an open issue as a method inducing a minimum amount of adverse effects, especially for patients who have failed other treatments.…”

Section: Vaccines For Pancreatic Cancermentioning

confidence: 99%

Adjuvant, neoadjuvant, and experimental regimens in overcoming pancreatic ductal adenocarcinoma

Wysocka

Kulbacka

Saczko

2016

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Pancreatic cancer is one of the most aggressive and deadly malignancies. Despite better understanding of its biology and pathogenesis, contemporary treatment regimens are still insufficient. Along with the introduction of new treatment agents and combination therapy, the response rates are increasing, but these scores do not go with overall survival, and results are frequently conflicting. Therefore, contemporary medicine faces the challenge of expanding the knowledge base and practice on all grounds – pathology, factor risk, diagnosis, and finally surgical and palliative treatment of this disease. This paper provides a review of current adjuvant and neoadjuvant regimens and the role of experimental therapies in pancreatic ductal adenocarcinoma.

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“…Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of tumor, with a five‐year survival rate of <5 % . PDAC is predicted to become the second leading cause of cancer‐related death in the USA by 2030 .…”

Section: Introductionmentioning

confidence: 99%

A Hydrogen Peroxide Activatable Gemcitabine Prodrug for the Selective Treatment of Pancreatic Ductal Adenocarcinoma

et al. 2019

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The main concern in the use of anticancer chemotherapeutic drugs is host toxicity. Patients need to interrupt or change chemotherapy due to adverse effects. In this study, we aimed to decrease adverse events with gemcitabine (GEM) in the treatment of pancreatic ductal adenocarcinoma and focused on the difference of hydrogen peroxide levels in normal versus cancer cells. We designed and synthesized a novel boronate‐ester‐caged prodrug that is activated by the high H2O2 concentrations found in cancer cells to release GEM. An H2O2‐activatable GEM (A‐GEM) has higher selectivity for H2O2 over other reactive oxygen species (ROS) and cytotoxic effects corresponding to the H2O2 concentration in vitro. A xenograft model of immunodeficient mice indicated that the effect of A‐GEM was not inferior to that of GEM when administered in vivo. In particular, myelosuppression was significantly decreased following A‐GEM treatment compared with that following GEM treatment.

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Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis?

Cited by 14 publications

References 60 publications

MicroRNA-155 Controls Exosome Synthesis and Promotes Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma

MicroRNA-155 Controls Exosome Synthesis and Promotes Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma

Adjuvant, neoadjuvant, and experimental regimens in overcoming pancreatic ductal adenocarcinoma

A Hydrogen Peroxide Activatable Gemcitabine Prodrug for the Selective Treatment of Pancreatic Ductal Adenocarcinoma

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