Translational applications of broad spectrum natural compounds and phytochemicals or their derivatives towards a novel treatment strategy for sarcomas

Abstract

Working to understand the genetic and phenotypic nature of sarcomas is Professor Kanya Honoki of the Department of Musculoskeltal Oncology and Reconstructive Medicine, Nara Medical University, Japan. "Current research is an extension of the concept from Getting To Know Cancer organization (Halifax, Canada) which I have joined in. Through this research, we are hoping to learn about the mechanisms and pathways which could be targetable by the compounds from natural sources, and whether this therapeutic approach could be feasible to the patients in variety of conditions such as a follow-up after conventional adjuvant treatment; in situations of the disease stages for which no accepted treatments exist; for patients who experience relapse or progression after targeted treatment; or in situations in which high-cost agents cannot be obtained, and we are also hoping our strategy could be feasible as an additive treatment to the conventional treatments in the initial stage." Honoki explains. Honoki and his team have been researching many aspects of physiology, genetics and transcriptomics in cancers seeking the targetable pathways/molecules, but currently have a particular focus on the metabolism and physiology of cancer stem cells (CSCs) in sarcomas. "The CSC theory suggests that, just as in other tissues, tumors have cells that provide a specific function and have differentiated in some way and cells that are capable of replicating and differentiating." observes Honoki. "Generally, it is thought that the CSCs are the hardiest cells within the tumor due to the flexibility in their gene expression." Honoki therefore attempted to isolate the CSCs from sarcomas so they could be characterized and potentially therapeutics screened against them. However, after significant effort he and his team found that there was no one definitive CSC. The population was, in fact heterogenetic, with different sets of genes being expressed and therefore different physiologies. Honoki considers the metabolism and physiology to be particularly important due to the heterogeneity of CSCs that he and his team discovered within sarcomas recently. Now, the research focus of his team is targeting the mechanisms of cellular metabolism, including oxidative phosphorylation and glycolysis, in sarcoma stem cells using the agents/compounds from natural resources to combat against this horrible disease.