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Autophagy Takes Center Stage as a Possible Cancer Hallmark.

ABSTRACT: Cancer remains one of the leading causes of death worldwide, despite significant advances in cancer research and improvements in anticancer therapies. One of the major obstacles to curing cancer is the difficulty of achieving the complete annihilation of resistant cancer cells. The resistance of cancer cells may not only be due to intrinsic factors or factors acquired during the evolution of the tumor but may also be caused by chemotherapeutic treatment failure. Conversely, autophagy is a conserved cellular process in which intracellular components, such as damaged organelles, aggregated or misfolded proteins and macromolecules, are degraded or recycled to maintain cellular homeostasis. Importantly, autophagy is an essential mechanism that plays a key role in tumor initiation and progression. Depending on the cellular context and microenvironmental conditions, autophagy acts as a double-edged sword, playing a role in inducing apoptosis or promoting cell survival. In this review, we propose several scenarios in which autophagy could contribute to cell survival or cell death. Moreover, a special focus on novel promising targets and therapeutic strategies based on autophagic resistant cells is presented.

SUBMITTER: Alvarez-Meythaler JG

PROVIDER: S-EPMC7643020 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Autophagy Takes Center Stage as a Possible Cancer Hallmark.

Alvarez-Meythaler Jose G JG Garcia-Mayea Yoelsis Y Mir Cristina C Kondoh Hiroshi H LLeonart Matilde E ME

Frontiers in oncology 20201022

Cancer remains one of the leading causes of death worldwide, despite significant advances in cancer research and improvements in anticancer therapies. One of the major obstacles to curing cancer is the difficulty of achieving the complete annihilation of resistant cancer cells. The resistance of cancer cells may not only be due to intrinsic factors or factors acquired during the evolution of the tumor but may also be caused by chemotherapeutic treatment failure. Conversely, autophagy is a conser ...[more]

PMID: 33194736

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Project description:Bipolar Disorder (BD) is a major psychiatric illness affecting up to 5% of the population. BD can progress over time to a chronic "neuroprogressive" course with cognitive and functional impairment. Currently, there are no validated predictors indicating which patients will develop a neuroprogressive course and there are no specific treatments. This review presents data supporting a novel hypothesis on the mechanisms underlying bipolar neuroprogression. Insulin resistance (IR) is present in 52% of BD patients and is associated with chronic course, treatment nonresponse, adverse brain changes and cognitive impairment. Further, bipolar morbidity increases 12-fold following the onset of IR indicating that IR may modify disease progression. I review evidence that IR is a testable and treatable modifying factor in neuroprogression and that reversing IR may be an efficient (and perhaps the only) means of obtaining remission in some patients. I draw a parallel with Helicobacter pylori in peptic ulcer disease (a novel mechanism that brought together two previously unrelated phenomena that uncovered a new treatment approach). This model of bipolar progression combines shared dysregulated mechanisms between IR and BD, allowing for early screening, case finding, and monitoring for neuroprogression, with the potential for intervention that could prevent advanced bipolar illness. KEY MESSAGES Neuroprogression in bipolar disorder is defined by a more severe form of illness and poor outcome. Currently, there are no validated predictors of neuroprogression, which could help inform treatment and improve prognosis. Insulin resistance is present in more than half of all bipolar patients and is associated with a chronic course of illness, lack of response to mood stabilizing treatment, cognitive impairment and poor functional outcomes. Insulin resistance may modify the course of bipolar disorder and promote neuroprogression. Insulin resistance may be a testable and potentially modifiable risk factor for neuroprogression in bipolar disorder.

Dataset Information

Autophagy Takes Center Stage as a Possible Cancer Hallmark.

Publications

Autophagy Takes Center Stage as a Possible Cancer Hallmark.

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