Drug repositioning in cancer: The current situation in Japan

Masuda, Takaaki; Tsuruda, Yusuke; Matsumoto, Yoshihiro; Uchida, Hajime; Nakayama, Keiichi I.; Mimori, Koshi

doi:10.1111/cas.14318

Cited by 30 publications

(21 citation statements)

References 67 publications

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“…We attempted to identify inhibitors of ASAP2 by a drug repositioning approach, a method for identifying new indications for existing approved drugs that can decrease the time and cost of development compared with traditional new drug discovery approaches 29‐31 . This has become a powerful strategy for developing anticancer agents 32 . Here, we employed the GPC method to comprehensively predict novel drug candidates based on chemically and genetically perturbed gene expression data 33 .…”

Section: Resultsmentioning

confidence: 99%

“…A, B, Niclosamide was identified as a compound for which the gene expression profiles induced by compound administration and ASAP2 knockout were correlated and the gene expression profiles induced by compound administration and ASAP2 overexpression were inversely correlated agents. 32 Here, we employed the GPC method to comprehensively predict novel drug candidates based on chemically and genetically perturbed gene expression data. 33 We evaluated 4 types of transcriptional correlations between chemically perturbed signatures and genetically perturbed signatures.…”

Section: Prediction Of Potential Inhibitors Of Asap2 By a Bioinformmentioning

confidence: 99%

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The novel driver gene ASAP2 is a potential druggable target in pancreatic cancer

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide, with a 5-y survival rate of 9%. 1 Genomic analyses of PDAC revealed that 4 common driver genes (KRAS, TP53, CDKN2A, and SMAD4), called the "big 4," are mutated with high frequencies, and many other genes are altered at lower frequencies, including potential clinical targets. Activating mutations in KRAS that occur early in tumorigenesis are observed frequently, and tend to be

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Section: Resultsmentioning

confidence: 99%

Section: Prediction Of Potential Inhibitors Of Asap2 By a Bioinformmentioning

confidence: 99%

The novel driver gene ASAP2 is a potential druggable target in pancreatic cancer

et al. 2021

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“…Regarding anti-allergic drugs, studies reported that breast cancer patients taking H1 antihistamines had better survival rates compared with those not taking H1 antihistamines [ 14 , 15 ]. Since the development of oncology drugs is a lengthy and costly process with high attrition rates, DR represents a powerful alternative strategy for the identification of effective treatments [ 16 ]. The benefits of DR are as follows: availability of pharmacokinetics, pharmacodynamics and posology data; knowledge of safety and toxicity, including rare adverse events; clinical experience derived from the original indications; widespread availability; low cost; and understanding of mechanisms of action and molecular targets [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Allergic Drug Suppressed Pancreatic Carcinogenesis via Down-Regulation of Cellular Proliferation

Kachi

Kato

Naiki‐Ito

et al. 2021

IJMS

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Pancreatic cancer is a fatal disease, and thus its chemoprevention is an important issue. Based on the recent report that patients with allergic diseases have a low risk for pancreatic cancer, we examined the potential chemopreventive effect of anti-allergic agents using a hamster pancreatic carcinogenesis model. Among the three anti-allergic drugs administered, montelukast showed a tendency to suppress the incidence of pancreatic cancer. Further animal study revealed a significantly decreased incidence of pancreatic cancer in the high-dose montelukast group compared with controls. The development of the pancreatic intraepithelial neoplasia lesions was also significantly suppressed. The Ki-67 labeling index was significantly lower in pancreatic carcinomas in the high-dose montelukast group than in controls. In vitro experiments revealed that montelukast suppressed proliferation of pancreatic cancer cells in a dose-dependent manner with decreased expression of phospho-ERK1/2. Montelukast induced G1 phase arrest. Conversely, leukotriene D4 (LTD4), an agonist of CYSLTR1, increased cellular proliferation of pancreatic cancer cells with an accumulation of phospho-ERK1/2. In our cohort, pancreatic ductal adenocarcinoma patients with high CYSLTR1 expression showed a significantly unfavorable clinical outcome compared with those with low expression. Our results indicate that montelukast exerts a chemopreventive effect on pancreatic cancer via the LTD4–CYSLTR1 axis and has potential for treatment of pancreatic carcinogenesis.

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“…Due to this lack of commercial interest, new uses for approved, off-patent medicines are mainly studied in independent clinical trials initiated and led by researchers from academia, research institutes or collaborative groups [15,16]. These trials are typically supported by public and philanthropic funds and aim to answer clinical questions that have an important impact on public health and patient needs but that are not addressed by industry-led trials [17,18].…”

Section: Introductionmentioning

confidence: 99%

Exploring new uses for existing drugs: innovative mechanisms to fund independent clinical research

Verbaanderd

Rooman

Huys

2021

Trials

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Background Finding new therapeutic uses for existing medicines could lead to safe, affordable and timely new treatment options for patients with high medical needs. However, due to a lack of economic incentives, pharmaceutical developers are rarely interested to invest in research with approved medicines, especially when they are out of basic patent or regulatory protection. Consequently, potential new uses for these medicines are mainly studied in independent clinical trials initiated and led by researchers from academia, research institutes, or collaborative groups. Yet, additional financial support is needed to conduct expensive phase III clinical trials to confirm the results from exploratory research. Methods In this study, scientific and grey literature was searched to identify and evaluate new mechanisms for funding clinical trials with repurposed medicines. Semi-structured interviews were conducted with 16 European stakeholders with expertise in clinical research, funding mechanisms and/or drug repurposing between November 2018 and February 2019 to consider the future perspectives of applying new funding mechanisms. Results Traditional grant funding awarded by government and philanthropic organisations or companies is well known and widely implemented in all research fields. In contrast, only little research has focused on the application potential of newer mechanisms to fund independent clinical research, such as social impact bonds, crowdfunding or public-private partnerships. Interviewees stated that there is a substantial need for additional financial support in health research, especially in areas where there is limited commercial interest. However, the implementation of new funding mechanisms is facing several practical and financial challenges, such as a lack of expertise and guidelines, high transaction costs and difficulties to measure health outcomes. Furthermore, interviewees highlighted the need for increased collaboration and centralisation at a European and international level to make clinical research more efficient and reduce the need for additional funding. Conclusions New funding mechanisms to support clinical research may become more important in the future but the unresolved issues identified in the current study warrant further exploration.

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Drug repositioning in cancer: The current situation in Japan

Cited by 30 publications

References 67 publications

The novel driver gene ASAP2 is a potential druggable target in pancreatic cancer

The novel driver gene ASAP2 is a potential druggable target in pancreatic cancer

Anti-Allergic Drug Suppressed Pancreatic Carcinogenesis via Down-Regulation of Cellular Proliferation

Exploring new uses for existing drugs: innovative mechanisms to fund independent clinical research

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