Paclitaxel, cisplatin and lonidamine in advanced ovarian cancer. A phase II study

Lena, M. De; Lorusso, Vito; Latorre, Agnese; Fanizza, Giuseppe; Gargano, G; Caporusso, L.; Guida, Michele; Catino, A.; Crucitta, E.; Sambiasi, D.; Mazzei, A.

doi:10.1016/s0959-8049(00)00400-7

Cited by 149 publications

(91 citation statements)

References 10 publications

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“…In human breast cancer MCF-7 cells, lonidamine enhances the cytotoxicity of several alkylating agents, including cisplatin, 4-hydroperoxycyclophosphamide, melphalan, and BCNU (Rosbe et al, 1989). The proven ability of lonidamine to inhibit energy metabolism in cancer cells and to enhance the activity of other anticancer agents has led to clinical trials (phase II-III) of this compound in combination with other anticancer agents for the treatment of breast cancer, glioblastoma multiforme, ovarian cancer, and lung cancer (De Lena et al, 2001;Di Cosimo et al, 2003;Oudard et al, 2003;Papaldo et al, 2003). Lonidamine (also known as TH-070) is also currently in phase II/III clinical trials for treatment of benign prostatic hyperplasia (BPH), given by oral drug administration.…”

Section: Lonidaminementioning

confidence: 99%

Glycolysis inhibition for anticancer treatment

et al. 2006

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Most cancer cells exhibit increased glycolysis and use this metabolic pathway for generation of ATP as a main source of their energy supply. This phenomenon is known as the Warburg effect and is considered as one of the most fundamental metabolic alterations during malignant transformation. In recent years, there are significant progresses in our understanding of the underlying mechanisms and the potential therapeutic implications. Biochemical and molecular studies suggest several possible mechanisms by which this metabolic alteration may evolve during cancer development. These mechanisms include mitochondrial defects and malfunction, adaptation to hypoxic tumor microenvironment, oncogenic signaling, and abnormal expression of metabolic enzymes. Importantly, the increased dependence of cancer cells on glycolytic pathway for ATP generation provides a biochemical basis for the design of therapeutic strategies to preferentially kill cancer cells by pharmacological inhibition of glycolysis. Several small molecules have emerged that exhibit promising anticancer activity in vitro and in vivo, as single agent or in combination with other therapeutic modalities. The glycolytic inhibitors are particularly effective against cancer cells with mitochondrial defects or under hypoxic conditions, which are frequently associated with cellular resistance to conventional anticancer drugs and radiation therapy. Because increased aerobic glycolysis is commonly seen in a wide spectrum of human cancers and hypoxia is present in most tumor microenvironment, development of novel glycolytic inhibitors as a new class of anticancer agents is likely to have broad therapeutic applications.

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Section: Lonidaminementioning

confidence: 99%

Glycolysis inhibition for anticancer treatment

et al. 2006

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“…Lonidamine has been shown to revert the resistance to cisplatin and to potentiate cisplatin activity in experimental models. This drug is undergoing clinical phase II trials for the treatment of ovarian carcinoma (de Lena et al, 2001). Lonidamine kills a diverse range of tumour cells in vitro (Angioli et al, 1997;Belzacq et al, 2001a).…”

Section: Ant Ligandsmentioning

confidence: 99%

Chemotherapy: targeting the mitochondrial cell death pathway

2002

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“…Lonidamine has been identified as an efficient HK inhibitor that specifically inhibits mitochondria-bound HK [47]. Several studies have demonstrated its anti-proliferative activities in monotherapies or in combination with other agents to improve cancer therapy in various types of cancers [48,49]. However, a Phase III clinical trial in patients with benign prostatic hyperplasia was terminated due to its hepatic toxicity [38].…”

Section: Targeting Aerobic Glycolysismentioning

confidence: 99%

The greedy nature of mutant RAS: a boon for drug discovery targeting cancer metabolism?

Lv¹,

Wang²,

Chang³

et al. 2016

ABBS

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RAS oncogene mutations are frequently detected in human cancers. Among RAS-mediated tumorigenesis, KRAS-driven cancers are the most frequently diagnosed and resistant to current therapies. Despite more than three decades of intensive efforts, there are still no specific therapies for mutant RAS proteins. While trying to block those well-established downstream pathways, such as the RAF-MAPK pathway and the PI3K-AKT pathway, attentions have been paid to potential effects of RAS on metabolic pathways and the feasibility for targeting these pathways. Recent studies have proved that RAS not only promotes aerobic glycolysis and glutamine metabolism reprograming to provide energy, but it also facilitates branched metabolism pathways, autophagy, and macropinocytosis. These alterations generate building blocks for tumor growth and strengthen antioxidant defense in tumor cells. All of these metabolic changes meet different demands of RAS-driven cancers, making them distinct from normal cells. Indeed, some achievements have been made to inhibit tumor growth through targeting specific metabolism rewiring in preclinical models. Although there is still a long way to elucidate the landscape of altered metabolism, we believe that specific metabolic enzymes or pathways could be therapeutically targeted for selective inhibition of RAS-driven cancers.

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Paclitaxel, cisplatin and lonidamine in advanced ovarian cancer. A phase II study

Cited by 149 publications

References 10 publications

Glycolysis inhibition for anticancer treatment

Glycolysis inhibition for anticancer treatment

Chemotherapy: targeting the mitochondrial cell death pathway

The greedy nature of mutant RAS: a boon for drug discovery targeting cancer metabolism?

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