The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Minjong; Lee, Ki Chang; Kim, Hyo Cheol; Yoon, Jung Hwan; Chung, Heesun; Park, Jae Hyung

doi:10.3348/kjr.2009.10.6.596

Cited by 34 publications

(19 citation statements)

References 29 publications

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“…Some small molecules such as 3-BP and lonidamine are direct inhibitors of HK enzyme. Preclinical studies demonstrate that 3-BP inhibits HK II in human cancer and is a promising anticancer drug targeting glycolysis [148, 149]. Lonidamine has completed phase III clinical trials in breast and lung cancers, and a trend for higher tumor responses and better survival parameters was observed when combined with chemotherapy [150, 173].…”

Section: Potential Targets For Tumor Therapymentioning

confidence: 99%

The sweet trap in tumors: aerobic glycolysis and potential targets for therapy

et al. 2016

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Metabolic change is one of the hallmarks of tumor, which has recently attracted a great of attention. One of main metabolic characteristics of tumor cells is the high level of glycolysis even in the presence of oxygen, known as aerobic glycolysis or the Warburg effect. The energy production is much less in glycolysis pathway than that in tricarboxylic acid cycle. The molecular mechanism of a high glycolytic flux in tumor cells remains unclear. A large amount of intermediates derived from glycolytic pathway could meet the biosynthetic requirements of the proliferating cells. Hypoxia-induced HIF-1α, PI3K-Akt-mTOR signaling pathway, and many other factors, such as oncogene activation and tumor suppressor inactivation, drive cancer cells to favor glycolysis over mitochondrial oxidation. Several small molecules targeting glycolytic pathway exhibit promising anticancer activity both in vitro and in vivo. In this review, we will focus on the latest progress in the regulation of aerobic glycolysis and discuss the potential targets for the tumor therapy.

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Section: Potential Targets For Tumor Therapymentioning

confidence: 99%

The sweet trap in tumors: aerobic glycolysis and potential targets for therapy

et al. 2016

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“…[92] More recent studies on animal models of human hepatoma reported a limited antitumor efficacy of 22 in vivo, which was associated to a certain hepatotoxicity. [93] At the present, there are no human ongoing clinical trials involving 22 , probably because of the lack of selective cytotoxic effects associated to its administration, as well as the low economic potential of this non patentable molecule.…”

Section: Glycolytic Effectors As Potential Targets In Cancer Therapymentioning

confidence: 99%

Anticancer Agents That Counteract Tumor Glycolysis

2012

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Can we consider cancer as a “metabolic disease”? Tumors are the result of a metabolic selection, forming tissues composed of heterogeneous cells that generally express an overactive metabolism as a common feature. In fact, cancer cells have to deal with increased needs for both energy and biosynthetic intermediates, in order to support their growth and invasiveness. However, their high proliferation rate often generates regions that are not sufficiently oxygenated. Therefore, their carbohydrate metabolism has to rely mostly on a glycolytic process that is uncoupled from oxidative phosphorylation. This metabolic switch, also known as the “Warburg Effect”, constitutes a fundamental adaptation of the tumor cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. As a result, tumor glycolysis may constitute an attractive target for cancer therapy. This approach has often raised concerns that anti-glycolytic agents may cause serious side effects on normal cells. Actually, the key for a selective action against cancer cells can be found in their hyperbolic addiction to glycolysis, which may be exploited to generate new anti-cancer drugs showing minimal toxicity. In fact, there is growing evidence that supports many glycolytic enzymes and transporters as suitable candidate targets for cancer therapy. Herein we review some of the most relevant anti-glycolytic agents that have been investigated so far for the treatment of cancer.

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“…HKI is the ubiquitously ex pressed isoform, whereas HKII is ex pressed in insulinsensitive tissues such as muscle and adipose (Robey and Hay, 2006). Many tumor cells overexpress HKII, and preclinical studies demonstrate that HKII inhibition could be an effective cancer therapy (Jae et al, 2009).…”

Section: Targets For Cancer Therapymentioning

confidence: 99%