Microregional antitumor activity of a small-molecule hypoxia-inducible factor 1 inhibitor

Okamoto, Kiyoshi; Ito, Daisuke; Miyazaki, Kensuke; Watanabe, Satoshi; Tohyama, Osamu; Yokoi, Akira; Ozawa, Yoichi; Asano, Makoto; Kawamura, Takanori; Yamane, Yoshinobu; Nagao, Seiji; Funasaka, Setsuo; Kamata, Junichi; Kotake, Yoshihiko; Aoki, Mika; Tsukahara, Naoko; Mizui, Yoshiharu; Tanaka, Isao; Sawada, Kohei

doi:10.3892/ijmm.2011.875

Cited by 9 publications

(14 citation statements)

References 27 publications

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“…The discovery of pathways essential for modulating stemness properties has contributed to the identification of several molecules that could eliminate GSCs, including new antineoplastic agents from natural sources [106][107][108][109][110][111][112][113]. A summary of current potential treatments is presented in Table 1 and Fig.…”

Section: Current Strategies Targeting Cancer Stem Cellsmentioning

confidence: 99%

Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

et al. 2021

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Glioblastoma (GBM) is the highest-grade form of glioma, as well as one of the most aggressive types of cancer, exhibiting rapid cellular growth and highly invasive behavior. Despite significant advances in diagnosis and therapy in recent decades, the outcomes for high-grade gliomas (WHO grades III-IV) remain unfavorable, with a median overall survival time of 15–18 months. The concept of cancer stem cells (CSCs) has emerged and provided new insight into GBM resistance and management. CSCs can self-renew and initiate tumor growth and are also responsible for tumor cell heterogeneity and the induction of systemic immunosuppression. The idea that GBM resistance could be dependent on innate differences in the sensitivity of clonogenic glial stem cells (GSCs) to chemotherapeutic drugs/radiation prompted the scientific community to rethink the understanding of GBM growth and therapies directed at eliminating these cells or modulating their stemness. This review aims to describe major intrinsic and extrinsic mechanisms that mediate chemoradioresistant GSCs and therapies based on antineoplastic agents from natural sources, derivatives, and synthetics used alone or in synergistic combination with conventional treatment. We will also address ongoing clinical trials focused on these promising targets. Although the development of effective therapy for GBM remains a major challenge in molecular oncology, GSC knowledge can offer new directions for a promising future.

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Section: Current Strategies Targeting Cancer Stem Cellsmentioning

confidence: 99%

Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

et al. 2021

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“…As a result, it achieved sustained HIF-1α suppression in xenograft gliomas in animal studies. Altogether, ER-400583-00 exhibited enhanced cytotoxicity against hypoxic glioma cells and enhanced antitumor activity in combination with radiation therapy (42). These findings indicate that inhibition of HIF-1α could provide new insights into the discovery of drugs for cancer treatment.…”

Section: Angiogenesis and Migration Are Linked To Hif-1α In The Develmentioning

confidence: 83%

Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme

Wang

et al. 2016

Oncology Reports

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Cell metabolism can be reprogrammed by tissue hypoxia leading to cell transformation and glioblastoma multiforme (GBM) progression. In response to hypoxia, GBM cells are able to express a transcription factor called hypoxia inducible factor-1 (HIF-1). HIF-1 belongs to a family of heterodimeric proteins that includes HIF-1α and HIF-1β subunits. HIF-1α has been reported to play a pivotal role in GBM development and progression. In the present review, we discuss the role of HIF-1α in glucose uptake, cancer proliferation, cell mobility and chemoresistance in GBM. Evidence from previous studies indicates that HIF-1α regulates angiogenesis, metabolic and transcriptional signaling pathways. Examples of such are the EGFR, PI3K/Akt and MAPK/ERK pathways. It affects cell migration and invasion by regulating glucose metabolism and growth in GBM cells. The present review focuses on the strategies through which to target HIF-1α and the related downstream genes highlighting their regulatory roles in angiogenesis, apoptosis, migration and glucose metabolism for the development of future GBM therapeutics. Combined treatment with inhibitors of HIF-1α and glycolysis may enhance antitumor effects in clinical settings.

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“…In animal models of HCC, tumor progression was associated with the up-regulation of HIF-1α and sequential production of VEGF. Thus, blockade of HIF-1 might be considered as a promising therapeutic approach in cancer treatment [164] . In a study by Zhang et al [165] , the expression levels of HIF-1α, together with SNAI1 and other EMT modulators, were assessed in a cohort of HCC patients.…”

Section: Angiogenic Factorsmentioning

confidence: 99%

Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials

Scaggiante

Kazemi

Pozzato

et al. 2014

WJG

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Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the sixth most common cancer worldwide and the third leading cause of cancer-related death. The difficulty to diagnose early cancer stages, the aggressive behaviors of HCC, and the poor effectiveness of therapeutic treatments, represent the reasons for the quite similar deaths per year and incidence number. Considering the fact that the diagnosis of HCC typically occurs in the advanced stages of the disease when the therapeutic options have only modest efficacy, the possibility to identify early diagnostic markers could be of significant benefit. So far, a large number of biomarkers have been associated to HCC progression and aggressiveness, but many of them turned out not to be of practical utility. This is the reason why active investigations are ongoing in this field. Given the huge amount of published works aimed at the identification of HCC biomarkers, in this review we mainly focused on the data published in the last year, with particular attention to the role of (1) molecular and biochemical cellular markers; (2) micro-interfering RNAs; (3) epigenetic variations; and (4) tumor stroma. It is worth mentioning that a significant number of the HCC markers described in the present review may be utilized also as targets for novel therapeutic approaches, indicating the tight relation between diagnosis and therapy. In conclusion, we believe that integrated researches among the different lines of investigation indicated above should represent the winning strategies to identify effective HCC markers and therapeutic targets.

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Microregional antitumor activity of a small-molecule hypoxia-inducible factor 1 inhibitor

Cited by 9 publications

References 27 publications

Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme

Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials

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