Resistance of cancer cells to chemotherapy is the first cause of cancer-associated death. Thus, new strategies to deal with the evasion of drug response and to improve clinical outcomes are needed. Genetic and epigenetic mechanisms associated with uncontrolled cell growth result in metabolism reprogramming. Cancer cells enhance anabolic pathways and acquire the ability to use different carbon sources besides glucose. An oxygen and nutrient-poor tumor microenvironment determines metabolic interactions among normal cells, cancer cells and the immune system giving rise to metabolically heterogeneous tumors which will partially respond to metabolic therapy. Here we go into the best-known cancer metabolic profiles and discuss several studies that reported tumors sensitization to chemotherapy by modulating metabolic pathways. Uncovering metabolic dependencies across different chemotherapy treatments could help to rationalize the use of metabolic modulators to overcome therapy resistance.

/pdf/metabolic-plasticity-in-chemotherapy-resistance-5e2w6c94yh.pdf

Metabolic Plasticity in Chemotherapy Resistance.

the education and training of the staff who will be involved in cytotoxic reconstitution which is followed by an invaluable chapter on the management of extrasavation of cytotoxic drugs. Section two of the book is likely to be a constant source of reference. It comprises a valuable alphabetical listing of monograhs of individual drugs that are used intravenously. Each monograph has been prepared by a named member of the working group according to a common structure. There is a section on nomenclature which includes the names of manufacturers and suppliers in the UK. There follows sections on chemistry, stability profile, clinical usage, details of how individual drugs are prepared for injection or infusion together with handling precautions. The final section considers how residual drug and contaminated articles should be destroyed. It should be emphasised that the working group has deliberately refrained from providing details of 'standard protocols for various indications'. In summary this is a book that should be read by any members of the 'Oncology Team' involved in setting up a reconstitution service. It should also be available in the departmental library of all Oncology Departments and all Pharmacies where any cytotoxic drugs are reconstituted and administered. This is a highly provocative book, written by two clinical radiotherapists, on the evolution of cancer. The authors base their approach to the treatment of cancer on the hypothesis that cancer represents a process of evolution in reverse, which they call 'devolution'. This concept is applied to develop theories on carcinogenesis, epidemiology, diagnosis and especially the strategy of cancer treatment. Fanconi's anaemia is cited as an evolutionary experiment of nature on carcinogenesis. The tumours described in patients with the DNA repair syndrome were classified according to their epithelial,-non-epithelial and gonadal origin. The early manifestation of non-malignancies and the later occurrence of epithelial tumours is considered as a support for the evolution theory. The cancer incidence in Japan following the explosion of the atomic bombs would also support this evolution theory. The parallel evolution of biology with the physicochemical alterations on earth are also cited in support of the evolution theory of cancer. Such arguments are then used for the formulation of a therapeutic strategy, starting with the repair of DNA damage, via carbohydrate biochemistry to immunotherapy and antiviral therapy. A large variety of arguments are used to formulate a strategy in surgery, radiotherapy, chemotherapy and immuno-therapy. For most readers of this book …

An Introduction to Radiobiology

Mesenchymal stem cells (MSCs) are pivotal to tissue homeostasis, repair, and regeneration due to their potential for self-renewal, multilineage differentiation, and immune modulation. Mitochondria are highly dynamic organelles that maintain their morphology via continuous fission and fusion, also known as mitochondrial dynamics. MSCs undergo specific mitochondrial dynamics during proliferation, migration, differentiation, apoptosis, or aging. Emerging evidence suggests that mitochondrial dynamics are key contributors to stem cell fate determination. The coordination of mitochondrial fission and fusion is crucial for cellular function and stress responses, while abnormal fission and/or fusion causes MSC dysfunction. This review focuses on the role of mitochondrial dynamics in MSC commitment under physiological and stress conditions. We highlight mechanistic insights into modulating mitochondrial dynamics and mitochondrial strategies for stem cell-based regenerative medicine. These findings shed light on the contribution of mitochondrial dynamics to MSC fate and MSC-based tissue repair.

/pdf/mitochondrial-dynamics-fission-and-fusion-in-fate-2iyf7byy0i.pdf

Mitochondrial Dynamics: Fission and Fusion in Fate Determination of Mesenchymal Stem Cells.

Microglia reprogram metabolic profiles for phenotype and function changes in central nervous system

The role of mitochondria in cancer formation and progression has been studied extensively, but much remains to be understood about this complex relationship. Mitochondria regulate many processes that are known to be altered in cancer cells, from metabolism to oxidative stress to apoptosis. Here, we review the evolving understanding of the role of mitochondria in cancer cells, and highlight key evidence supporting the role of mitochondria in cancer immune evasion and the effects of mitochondria-targeted antitumor therapy. Also considered is how knowledge of the role of mitochondria in cancer can be used to design and improve cancer therapies, particularly immunotherapy and radiation therapy. We further offer critical insights into the mechanisms by which mitochondria influence tumor immune responses, not only in cancer cells but also in immune cells. Given the central role of mitochondria in the complex interactions between cancer and the immune system, high priority should be placed on developing rational strategies to address mitochondria as potential targets in future preclinical and clinical studies. We believe that targeting mitochondria may provide additional opportunities in the development of novel antitumor therapeutics.

/pdf/role-of-mitochondria-in-cancer-immune-evasion-and-potential-1vk09jqbxi.pdf

Role of Mitochondria in Cancer Immune Evasion and Potential Therapeutic Approaches.

Elevated metabolism is a key hallmark of multiple cancers, serving to fulfill high anabolic demands. Ovarian cancer (OVCA) is the fifth leading cause of cancer deaths in women with a high mortality rate (45%). Chemoresistance is a major hurdle for OVCA treatment. Although substantial evidence suggests that metabolic reprogramming contributes to anti-apoptosis and the metastasis of multiple cancers, the link between tumor metabolism and chemoresistance in OVCA remains unknown. While clinical trials targeting metabolic reprogramming alone have been met with limited success, the synergistic effect of inhibiting tumor-specific metabolism with traditional chemotherapy warrants further examination, particularly in OVCA. This review summarizes the role of key glycolytic enzymes and other metabolic synthesis pathways in the progression of cancer and chemoresistance in OVCA. Within this context, mitochondrial dynamics (fission, fusion and cristae structure) are addressed regarding their roles in controlling metabolism and apoptosis, closely associated with chemosensitivity. The roles of multiple key oncogenes (Akt, HIF-1α) and tumor suppressors (p53, PTEN) in metabolic regulation are also described. Next, this review summarizes recent research of metabolism and future direction. Finally, we examine clinical drugs and inhibitors to target glycolytic metabolism, as well as the rationale for such strategies as potential therapeutics to overcome chemoresistant OVCA.

/pdf/tumor-metabolism-regulating-chemosensitivity-in-ovarian-2700umnnzy.pdf

Tumor metabolism regulating chemosensitivity in ovarian cancer

Altered mitochondrial fusion drives defensive glutathione synthesis in cells able to switch to glycolytic ATP production.

Mitochondria are highly dynamic organelles that respond rapidly to a number of stressors to regulate energy transduction, cell death signaling, and reactive oxygen species generation. We hypothesiz...

David A. Patten

Papers

Tumor metabolism regulating chemosensitivity in ovarian cancer

Altered mitochondrial fusion drives defensive glutathione synthesis in cells able to switch to glycolytic ATP production.

Mitochondrial adaptation in human mesenchymal stem cells following ionizing radiation.