Drug resistance in pancreatic cancer: Impact of altered energy metabolism

Grasso, Cristoforo; Jansen, Gerrit; Giovannetti, Elisa

doi:10.1016/j.critrevonc.2017.03.026

Cited by 208 publications

(170 citation statements)

References 142 publications

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“…This process is known as Warburg effect [18,28]. In addition, during the last years, many articles have appeared indicating the Warburg effect may be potentially related with drug resistance treatment in cancer [14,29,30]. Therefore, in this study, we have evaluated the potential metabolic changes that occur in BCC cells resistant to PDT, associating the resistance with a glycolytic metabolism.…”

Section: Discussionmentioning

confidence: 99%

Metformin as an Adjuvant to Photodynamic Therapy in Resistant Basal Cell Carcinoma Cells

Mascaraque

Delgado-Wicke

Nuevo‐Tapioles

et al. 2020

Cancers

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Photodynamic Therapy (PDT) with methyl-aminolevulinate (MAL-PDT) is being used for the treatment of Basal Cell Carcinoma (BCC), although resistant cells may appear. Normal differentiated cells depend primarily on mitochondrial oxidative phosphorylation (OXPHOS) to generate energy, but cancer cells switch this metabolism to aerobic glycolysis (Warburg effect), influencing the response to therapies. We have analyzed the expression of metabolic markers (β-F1-ATPase/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio, pyruvate kinase M2 (PKM2), oxygen consume ratio, and lactate extracellular production) in the resistance to PDT of mouse BCC cell lines (named ASZ and CSZ, heterozygous for ptch1). We have also evaluated the ability of metformin (Metf), an antidiabetic type II compound that acts through inhibition of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway to sensitize resistant cells to PDT. The results obtained indicated that resistant cells showed an aerobic glycolysis metabolism. The treatment with Metf induced arrest in the G0/G1 phase and a reduction in the lactate extracellular production in all cell lines. The addition of Metf to MAL-PDT improved the cytotoxic effect on parental and resistant cells, which was not dependent on the PS protoporphyrin IX (PpIX) production. After Metf + MAL-PDT treatment, activation of pAMPK was detected, suppressing the mTOR pathway in most of the cells. Enhanced PDT-response with Metf was also observed in ASZ tumors. In conclusion, Metf increased the response to MAL-PDT in murine BCC cells resistant to PDT with aerobic glycolysis.

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Section: Discussionmentioning

confidence: 99%

Metformin as an Adjuvant to Photodynamic Therapy in Resistant Basal Cell Carcinoma Cells

Mascaraque

Delgado-Wicke

Nuevo‐Tapioles

et al. 2020

Cancers

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“…In PDAC, the expression of this oncogene is associated with a reduced efficacy of therapeutic agents and to a metabolic shift toward anabolic metabolism . The latter further contributes to acquired chemoresistance . As such, alteration of this metabolic way is taken into account for therapeutic purposes.…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor beta‐induced, an extracellular matrix interacting protein, enhances glycolysis and promotes pancreatic cancer cell migration

Costanza

Rademaker

Tiamiou

et al. 2019

Intl Journal of Cancer

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Pancreatic ductal adenocarcinoma (PDAC) remains a deadly malignancy with no efficient therapy available up-to-date. Glycolysis is the main provider of energetic substrates to sustain cancer dissemination of PDAC. Accordingly, altering the glycolytic pathway is foreseen as a sound approach to trigger pancreatic cancer regression. Here, we show for the first time that high transforming growth factor beta-induced (TGFBI) expression in PDAC patients is associated with a poor outcome. We demonstrate that, although usually secreted by stromal cells, PDAC cells synthesize and secrete TGFBI in quantity correlated with their migratory capacity. Mechanistically, we show that TGFBI activates focal adhesion kinase signaling pathway through its binding to integrin αVβ5, leading to a significant enhancement of glycolysis and to the acquisition of an invasive phenotype. Finally, we show that TGFBI silencing significantly inhibits PDAC tumor development in a chick chorioallantoic membrane assay model. Our study highlights TGFBI as an oncogenic extracellular matrix interacting protein that bears the potential to serve as a target for new anti-PDAC therapeutic strategies.

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“…Therefore, FF forming in tumor stroma demonstrates the high aggressiveness of carcinoma (Van den Eynden et al 2008). The tumor interstitial fibrosis associated with the adverse prognosis and anti-tumor drug resistance (Grasso et al 2017) has been observed in the carcinoma of breast cancer, pancreatic cancer (Thomas & Radhakrishnan 2019), colorectal cancer (Ikuta et al 2018), and gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "Association between the degree of fibrosis in fibrotic focus and the unfavorable clinicopathological prognostic features of breast cancer (v0.1)"

2019

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To explore the association between the degree of fibrosis in fibrotic focus (FF) and the unfavorable clinicоpathological prognostic features of breast cancer. Methods. 169 cases of breast invasive ductal carcinoma (IDC) were included in the study. Hematoxylin and eosin (H&E) staining was performed in the primary lesion of breast IDC and the degree of fibrosis in tumor-stromal FF was assessed. The association between the degree of fibrosis in FF and the well-known clinicopathologicfeatures of breast cancer was investigated and the influence of the degree of fibrosis in FF on the survival was analyzed. Results. Tumor size > 2cm (P = 0.023), vascular invasion (P = 0.011), lymphatic vessel invasion (P < 0.001) and HER-2+ (P = 0.032) were positively correlated with the degree of fibrosis in FF in breast IDC. The result of multivariate analysis showed that lymphatic vessel invasion was the only independent correlation factor of high fibrosis in FF in breast IDC (OR = 3.82, 95% CI 1.13 ~12.82, P = 0.031). The Nottingham prognostic index (NPI) of high fibrosis in FF was significantly higher than that of mild and moderate fibrosis in FF in the no vascular infiltration subgroup, the no nerve infiltration subgroup, and the Luminal A subgroup (P = 0.014, 0.039, and 0.018; respectively). Conclusions. The high fibrosis in FF is closely associated with the strong invasiveness and the high malignancy of breast IDC. The degree of fibrosis in FF might be considered as a very practical and meaningful pathological feature of breast cancer.

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Drug resistance in pancreatic cancer: Impact of altered energy metabolism

Cited by 208 publications

References 142 publications

Metformin as an Adjuvant to Photodynamic Therapy in Resistant Basal Cell Carcinoma Cells

Metformin as an Adjuvant to Photodynamic Therapy in Resistant Basal Cell Carcinoma Cells

Transforming growth factor beta‐induced, an extracellular matrix interacting protein, enhances glycolysis and promotes pancreatic cancer cell migration

Peer Review #1 of "Association between the degree of fibrosis in fibrotic focus and the unfavorable clinicopathological prognostic features of breast cancer (v0.1)"

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