Glycolysis inhibition as a cancer treatment and its role in an anti-tumour immune response.

Increased glycolysis is the main source of energy supply in cancer cells that use this metabolic pathway for ATP generation. Altered energy metabolism is a biochemical fingerprint of cancer cells that represents one of the "hallmarks of cancer". The immune system can prevent tumour growth by eliminating cancer cells but this editing process ultimately results in poorly immunogenic cells remaining allowing for unchallenged tumour growth. In this review we look at the glycolysis pathway as a target for cancer treatments. We also examine the interplay between the glycolysis modulation and the immune response as an anti-cancer therapy.

Combination of electroporation delivered metabolic modulators with low-dose chemotherapy in osteosarcoma.

BACKGROUND: Osteosarcoma accounts for roughly 60% of all malignant bone tumors in children and young adults. The five-year survival rate for localized tumors after surgery and chemotherapy is approximately 70% whilst it drastically reduces to 15-30% in metastatic cases. Metabolic modulation is known to increase sensitivity of cancers to chemotherapy. A novel treatment strategy in Osteosarcoma is needed to battle this devastating malady. RESULTS: Electroporation-delivered metabolic modulators were more effective in halting the cell cycle of Osteosarcoma cells and this negatively affects their ability to recover and proliferate, as shown in colony formation assays. Electroporation-delivered metabolic modulators increase the sensitivity of Osteosarcoma cells to chemotherapy and this combination reduces their survivability. CONCLUSION: This novel treatment approach highlights the efficacy of electroporation in the delivery of metabolic modulators in Osteosarcoma cells, and increased sensitivity to chemotherapy allowing for a lower dose to be therapeutic. METHODS: Metabolic modulations of two Osteosarcoma cell lines were performed with clinically available modulators delivered using electroporation, and its combination with low-dose Cisplatin. The effects of Dicholoroacetic acid, 2-Deoxy-D-glucose and Metformin on cell cycle and recovery of Osteosarcoma cells were assessed. Their sensitivity to chemotherapy was also assessed when treated in combination with electroporation-delivered metabolic modulators.

Expressional changes in stemness markers post electrochemotherapy in pancreatic cancer cells.

Pancreatic cancer is one of the most lethal cancers with high metastatic potential and strong chemoresistance. The capability of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. Cancer stem cells exhibit great tumorigenicity and are closely correlated with drug resistance and tumor recurrence. The aim of our study was to illustrate electrochemotherapy as an effective treatment for pancreatic cancer along with the expression change in stemness genes (Nanog, Sox2 and Oct3/4) in pancreatic cancer cells post electrochemotherapy with bleomycin, cisplatin and oxaliplatin. Our results showed the enhanced expression of Nanog and decreased expression level of Oct3/4 after electrochemotherpy. We thus propose that these stemness markerS may have important roles in the initiation and/or recurrence of pancreatic cancer, and consequently may serve as important molecular diagnostics and/or therapeutic targets for the development of novel treatment strategies in pancreatic cancer patients. In conclusion, targeting these stemness factors could potentially improve electrochemotherapy as a treatment and preventing recurrence.