Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies

Abstract

Tumor relapse represents one of the main obstacles to cancer treatment. Many patients experience cancer relapse even decades from the primary tumor eradication, developing more aggressive and metastatic disease. This phenomenon is associated with the emergence of dormant cancer cells, characterized by cell cycle arrest and largely insensitive to conventional anti-cancer therapies. These rare and elusive cells may regain proliferative abilities upon the induction of cell-intrinsic and extrinsic factors, thus fueling tumor re-growth and metastasis formation. The molecular mechanisms underlying the maintenance of resistant dormant cells and their awakening are intriguing but, currently, still largely unknown. However, increasing evidence recently underlined a strong dependency of cell cycle progression to metabolic adaptations of cancer cells. Even if dormant cells are frequently characterized by a general metabolic slowdown and an increased ability to cope with oxidative stress, different factors, such as extracellular matrix composition, stromal cells influence, and nutrient availability, may dictate specific changes in dormant cells, finally resulting in tumor relapse. The main topic of this review is deciphering the role of the metabolic pathways involved in tumor cells dormancy to provide new strategies for selectively targeting these cells to prevent fatal recurrence and maximize therapeutic benefit.

Viscoelastic Liquid Matrix with Faster Bulk Relaxation Time Reinforces the Cell Cycle Arrest Induction of the Breast Cancer Cells via Oxidative Stress

“…Using the viscoelastic liquid substrate to investigate the matrix viscous component-induced dormancy of breast cancer cells is advantageous in generating viable multicellular aggregates. Dormant cells are viable cells with low metabolic activity and ceased proliferation ability [ 51 , 52 ]. The ultralow adhesive cell surface can promote the formation of compact 3-D multicellular aggregates, nevertheless with a necrotic core.…”

A Spectroscopic Technique to Simultaneously Characterize Fatty Acid Uptake, Mitochondrial Activity, Vascularity, and Oxygen Saturation for Longitudinal Studies In Vivo

“…We have developed an optical toolkit to characterize major relevant axes of cancer metabolism longitudinally in vivo. Simultaneous spectroscopy of TMRE and Bodipy FL 16 along with vascular endpoints is well poised to provide insight into metabolic plasticity and, therefore, can be readily applied to longitudinal studies of treatment resistance and recurrence—two outstanding challenges in cancer therapy [ 33 ]. With work pointing to the increased role of lipid metabolism in residual tumor cells [ 13 ] and the plasticity of mitochondrial function throughout tumor progression [ 34 ], simultaneous, longitudinal measurements of these two critical endpoints will allow for a more complete understanding of the interplay of these two processes.…”

Advances in the molecular regulation mechanism of tumor dormancy and its therapeutic strategy

“…Dormancy represents a fundamental survival strategy employed by organisms to endure adverse conditions, thereby conferring a selective advantage [ 25 ]. In the context of tumors, the utilization of dormancy serves as a conservative mechanism to enhance resistance against anticancer drugs, allowing tumor cells to withstand the onslaught of chemotherapy and subsequent clearance attempts, thereby ensuring their survival.…”