About this Research Topic
Cancer cell proliferation requires up-regulation and rewiring of metabolic pathways to feed anabolic cell growth. Oncogenic drivers directly and indirectly regulate metabolic pathways. Aberrant metabolism is central not only for leukemia cells proliferation and survival, but also mediates development of metastasis and resistance to targeted therapies. It is now undeniable the relevant role of metabolic mechanisms in leukemogenesis with significant implications for the development of target therapies. Abnormality of lipid promotes leukemia development, invasion and metastasis via multiple signaling pathways, which implies that targeting lipid metabolism could be a novel strategy for cancer prevention and treatment.
A key difference in metabolism between normally proliferating and leukemic cells is the loss of integrity of normal feedback regulatory loops in leukemic Stem Cells (LSCs). In normal cells, proliferative signals are counter-balanced by growth suppressive signals. This balance is influenced by the interaction between growth factors and nutrients in the cellular microenvironment. The ability of LSCs to adjust their metabolic state – their metabolic plasticity – likely decides how they contribute to tumor progression and relapse. Fatty acid oxidation has been reported to modulate the threshold for apoptosis and regulate quiescence in leukemic progenitors. LSCs develop resistance in part by increasing fatty acid oxidation and thus, not surprisingly, obesity is emerging as a major risk factor. This provides rationale for supportive therapeutic measures through nutritional intervention. Prostaglandin E2 (PGE2), has been demonstrated to promote tumor progression through induction and maintenance of myeloid derived suppressor cells (MDSC). Targeting lipid mediators may represent a novel therapeutic approach. A strong motivation for this Research Topic is therefore to begin building a repository where all these new observations may be shared, compared and contextualized. This will pave the way for a coherent structural framework to develop knowledge on metabolism and cancer in the context of developing new therapies.
The links between metabolism and leukemia are multifaceted. Ongoing, mechanistic insights into the links between metabolism, genetics and immunologic status are expected to inform selection of one or more therapies that can converge on metabolic vulnerabilities resulting in elimination of SCLs.
In this view, we solicit the participation of Researchers active in the area of clinical, translational studies, basic biology research, theoretical modelling, innovative technological tools, pharmacology and drug design. We welcome submissions of the following article types: Case Report, Clinical Trial, General Commentary, Hypothesis and Theory, Mini Review, Original Research, Perspective, Review, and Systematic Review on the following topics (but not limited to):
· Epigenetics alterations the relation with the control of metabolic pathways
· Metabolic reprogramming associated to recurrent genetic alterations in leukemias
· Metabolic crosstalk between leukemic cells, microenvironment and immune system
· Emerging therapeutic opportunities related to metabolic alterations to personalized therapies
· Novel technical approach to study Metabolism
Keywords: Leukemia, OXPHOS and Glycolysis, Mitochondria, ROS, Metabolic Reprogramming
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