Special Issue "Metabolic Reprogramming and Vulnerabilities in Cancer"
A special issue of Cancers (ISSN 2072-6694).
Deadline for manuscript submissions: closed (15 April 2019)
Dr. Deepak Nagrath
Department of Biomedical Engineering, Department of Chemical Engineering, University of Michigan, NCRC, Bldg 28, Room 3048W, 2800 Plymouth Rd, Ann Arbor, MI 48109, USA
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Interests: cancer metabolism; tumor microenvironment; metabolic profiling; systems biology; metabolomics
Dr. Costas Lyssiotis
Department of Molecular and Integrative Physiology; Division of Gastroenterology, Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan Room 6308, 1150 East Medical Center Drive, Ann Arbor, MI 48109, USA
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Interests: : tumor metabolism; pancreatic cancer; metabolomics; stromal metabolism; immunometabolism
The dysregulated metabolic traits of cancer are not confined to malignant cells; solid tumors systemically reprogram their metabolism to create a unique metabolic microenvironment to sustain tumorigenic properties. Alterations in extrinsic and intrinsic signals in tumors dictate how metabolic rewiring occurs. Rewired metabolism not only provides a selective advantage to malignant cells in nutrient-stressed and hypoxic environments, but also facilitates invasion, metastasis, immune suppression, drug resistance, and tumor-promoting epigenetic modifications. However, recent studies have highlighted an inherent complexity of dissecting metabolic mechanisms driving tumorigenesis. One aspect of this complexity is due to the impact of metabolic alterations on epigenetic modifications and DNA damage repair. Metabolic pathways responsible for regulating methyl and acetyl levels create a reciprocal feedback loop between metabolism and genetic reprogramming in tumors. We expect new studies elucidating how tumors rewire to provide substrates for chromatin regulation. Further, with the increasing interest in mitochondrial metabolism and its role as a signaling organelle, we expect studies focused on the effect of ROS on DNA damage, and regulation of NAD metabolism for sirtuin-mediated DNA damage repair.
The other aspect of complexity in metabolic reprogramming is due to intratumoral heterogeneity. Reactive stroma are important players in the metabolic interactions within the tumor microenvironment (TME). Cancer cells reprogram stromal cells to help meet there high bioenergetic demands via secreted metabolites, exosomes, proteins, and lipids. Rewired cancer metabolism can also create an immunosuppressive microenvironment that actively inhibits the antitumor response of T-cells and natural killer cells. Therefore, there is a growing interest in reversing the tumor-supporting properties of reactive stroma for therapeutic benefits. New studies are expected to focus on modulating stromal metabolism to improve immunotherapy response or inhibit pathways supporting cancer metabolism. The unique composition of the TME has also come under scientific scrutiny leading to the discovery of cancer cells utilizing exosomes, extracellular proteins and apoptotic bodies as fuel sources. We expect novel studies on non-canonical nutrient sources that can be selectively targeted in cancer cells. Thus, strategies targeting TME metabolism have the potential to elicit a systemic anti-tumor response in contrast to cancer-specific targets of antineoplastic drugs.
Contemporary research has demonstrated that the influence of cancer metabolism on the portfolio of cancer hallmarks is prevalent and has proven that it can be used to our advantage. Discovering and dissecting tumor-specific metabolic mechanisms will open new avenues of targeting metabolic vulnerabilities in cancers. In summary, this issue will highlight emerging aspects of metabolic reprogramming on tumor phenotype with a focus on exploiting these idiosyncratic metabolic mechanisms for therapeutic benefit.
Dr. Deepak Nagrath
Dr. Costas Lyssiotis
Manuscript Submission Information
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