Cellular and Metabolic Reprogramming in Cancer

Dear Colleagues,

Cancer is a heterogeneous disease caused by genetic and epigenetic changes conferring characteristic properties to cancer cells, including enhanced cell proliferation, immortality, resistance to cell death, the ability to migrate and invade adjacent tissues, and metastasise to distant sites in the body. The tumour microenvironment, consisting of stromal cells, such as cancer-associated fibroblasts, innate immune cells and vascular cells, and the extracellular matrix (ECM) components play an integral role in tumour initiation and progression. The dynamic mutual interactions between cancer cells and their microenvironment allow cancer cells to grow and survive; they stimulate cancer cell heterogeneity and increase the multidrug resistance leading to cancer cell progression and metastasis.

The acquisition of the hallmarks of cancer during cancer evolution from normal to malignant and metastatic cancer cells involves several phenotypic changes for the cells to survive, grow, and thrive, often in harsh microenvironments with limited nutrient and oxygen supplies, which is referred to as cancer cell reprogramming. Cancer cell reprogramming occurs due to both genetic and non-genetic factors and is accompanied by many changes and adaptations, including metabolic reprogramming that acts as a driver of carcinogenesis.

Cancer cells have the capability to modify and reprogram their cellular metabolism in order to support biomass production and proliferation. The alterations in metabolite levels affect gene and protein expression, cellular differentiation, and the non-transformed cells in the tumour microenvironment.

There is also a dynamic interplay between metabolism and epigenetics. Changes in the levels of metabolites affect the addition and removal of epigenetic marks and, thus, gene expression. The regulation of gene expression in response to fluctuations in metabolite levels is critical for the survival of all organisms. Physiologically, the epigenetic and chromatin responses to metabolism that influence gene expression are important for sensing the environmental changes, such as nutrient and oxygen availability allowing cells to adopt. In pathological states, the connection between metabolic processes and epigenetic and chromatin responses mediates altered gene expression in complex disease, such as ageing/senescence and cancer. Importantly, mutations in metabolic enzymes and chromatin-modifying complexes underlie complex human diseases affecting multiple organs.

Although metabolism is a fundamental cellular process, it can become harmful for cells by leading to DNA damage, e.g., by an increase in oxidative stress or the generation of toxic byproducts. To deal with such insults, cells activate DNA damage response (DDR) pathways that allow for the maintenance of genome integrity.

Cellular and metabolic reprogramming can occur in response to both intracellular and extracellular signals, including growth factors and cytokines, ECM remodelling and chronic inflammation. Cellular and metabolic reprogramming contributes to acquired drug resistance to anti-cancer agents, significantly limiting patient survival.

The purpose of this Special Issue is to focus on cutting edge research and cover advances on cellular and metabolic reprogramming in malignancies, including cancer stem cells and differentiation, extracellular matrix remodeling, metabolic switches, and anticancer strategies, their therapeutic potential, benefits, possible complications, and pitfalls of such approaches. We invite authors to submit original and novel review articles on basic and translational research.

Dr. Evangelos Kolettas
Dr. Maria Georgiadou
Dr. Eugenia Roupakia
Guest Editors

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• cancer
• stem cells
• differentiation
• cellular reprogramming
• metabolic reprogramming/adaptation