Facts and Perspectives: Implications of tumor glycolysis on immunotherapy response in triple negative breast cancer

Schreier, Ashley; Zappasodi, Roberta; Serganova, Inna; Brown, Kristy A.; Demaria, Sandra; Andreopoulou, Eleni

doi:10.3389/fonc.2022.1061789

Cited by 5 publications

(5 citation statements)

References 141 publications

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“…Due to metabolic reprogramming, cancer cells exhibit high glycolysis rates, resulting in lactate overproduction and increased extracellular acidity [ 18 ]. In addition, tumor glycolysis and lactate production affect the tumor immune microenvironment through metabolic competition with infiltrating immune cells [ 19 ]. Therefore, targeting glycolysis has become a promising direction for tumor therapy.…”

Section: Discussionmentioning

confidence: 99%

hsa_circ_0003596, as a novel oncogene, regulates the malignant behavior of renal cell carcinoma by modulating glycolysis

Xie,

Qin,

Luo

et al. 2023

Eur J Med Res

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Background This research was planned to analyze hsa_circ_0003596 (circCOL5A1) and glycolysis-focused mechanisms in renal cell carcinoma (RCC). Methods circCOL5A1, miR-370-5p, and PRKCSH levels were determined in RCC tissues and selected cell lines by RT-qPCR and/or Western blot. RCC cells after corresponding transfection were tested by colony formation assay, EdU assay, Transwell assay, and flow cytometry to analyze cell proliferation, invasion, migration, and apoptosis. Meanwhile, glycolysis in cells was evaluated by measuring glucose consumption, lactic acid, and ATP production, as well as immunoblotting for HK2 and PKM2. In addition, circCOL5A1 knockdown was performed in animal experiments to observe tumor growth and glycolysis. Finally, the ceRNA network between circCOL5A1, miR-370-5p, and PRKCSH was studied by luciferase reporter assay and RIP experiment. Results circCOL5A1 and PRKCSH were highly expressed and miR-370-5p was poorly expressed in RCC. circCOL5A1 knockdown depressed RCC proliferation, invasion, migration, and glycolysis, and enhanced apoptosis. circCOL5A1 competitively adsorbed miR-370-5p. Artificial upregulation of miR-370-5p saved the pro-tumor effect of circCOL5A1 on RCC cells, as evidenced by suppression of tumor malignancy and glycolysis. miR-370-5p targeted PRKCSH. PRKCSH overexpression contributed to a reversal of the anti-tumor effect of circCOL5A1 silencing. Silencing circCOL5A1 inhibited RCC tumor growth and glycolysis. Conclusions circCOL5A1 regulates the malignant behavior of RCC by modulating glycolysis.

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Section: Discussionmentioning

confidence: 99%

hsa_circ_0003596, as a novel oncogene, regulates the malignant behavior of renal cell carcinoma by modulating glycolysis

Xie,

Qin,

Luo

et al. 2023

Eur J Med Res

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“…Breast cancer is a predominantly glycolytic malignancy [150] involved in tumor progression [151] and resistance to therapy [152]. Supporting these observations are the experiments of Godoy et al [153] who found that 90% of breast cancers had a high or very high expression of the glucose transporter 1 and 2 (GLUT1, GLUT2) which means that they have a high glycolytic flux.…”

Section: Breast Cancermentioning

confidence: 95%

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Koltai,

Fliegel

2024

Preprint

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Rarely has a chemical elicited as much controversy as has dichloroacetate (DCA). DCA was initially considered a dangerous toxic industrial waste product. Then it was a potential treatment for lactic acidosis. However, the main controversies started in 2008 when DCA was found to have anti-cancer effects in experimental animals. These publications showed contradictory results in vivo and in vitro, so that a thorough consideration of this compound in cancer is merited. Despite 50 years of experimentation, DCA’s future in therapeutics is uncertain. Without adequate clinical trials and lack of health authorities’ approval, DCA has been introduced in off -label cancer treatments in alternative medicine clinics in Canada, Germany, and other European countries. The lack of well-planned clinical trials and its use by people without medical training has discouraged consideration by the scientific community. There are limited thorough clinical studies of DCA, and many publications are individual case reports. Case reports of DCA benefits against cancer have been increasing recently. Furthermore, it has been shown that DCA synergizes with conventional treatments and other repurposable drugs. Beyond the classic DCA target, pyruvate dehydrogenase kinase, new target molecules have also been recently discovered. These findings have renewed interest in DCA. This paper explores whether existing evidence justifies further research on DCA for cancer treatment and it explores the role DCA may play in oncology treatment.

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“…Breast cancer is a malignancy characterized predominantly by glycolytic metabolism [ 150 ], which is involved in tumor progression [ 151 ] and resistance to therapy [ 152 ]. Supporting these observations are the experiments of Godoy et al [ 153 ], who found that 90% of breast cancers had high or very high expression of glucose transporters 1 and 2 (GLUT1 and GLUT2), which means that they have a high glycolytic flux.…”

Section: Experimental Evidence For Dca Activity In Cancermentioning

confidence: 99%

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Koltai,

Fliegel

2024

Pharmaceuticals

View full text Add to dashboard Cite

Rarely has a chemical elicited as much controversy as dichloroacetate (DCA). DCA was initially considered a dangerous toxic industrial waste product, then a potential treatment for lactic acidosis. However, the main controversies started in 2008 when DCA was found to have anti-cancer effects on experimental animals. These publications showed contradictory results in vivo and in vitro such that a thorough consideration of this compound’s in cancer is merited. Despite 50 years of experimentation, DCA’s future in therapeutics is uncertain. Without adequate clinical trials and health authorities’ approval, DCA has been introduced in off-label cancer treatments in alternative medicine clinics in Canada, Germany, and other European countries. The lack of well-planned clinical trials and its use by people without medical training has discouraged consideration by the scientific community. There are few thorough clinical studies of DCA, and many publications are individual case reports. Case reports of DCA’s benefits against cancer have been increasing recently. Furthermore, it has been shown that DCA synergizes with conventional treatments and other repurposable drugs. Beyond the classic DCA target, pyruvate dehydrogenase kinase, new target molecules have also been recently discovered. These findings have renewed interest in DCA. This paper explores whether existing evidence justifies further research on DCA for cancer treatment and it explores the role DCA may play in it.

show abstract

Facts and Perspectives: Implications of tumor glycolysis on immunotherapy response in triple negative breast cancer

Cited by 5 publications

References 141 publications

hsa_circ_0003596, as a novel oncogene, regulates the malignant behavior of renal cell carcinoma by modulating glycolysis

hsa_circ_0003596, as a novel oncogene, regulates the malignant behavior of renal cell carcinoma by modulating glycolysis

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

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