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Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy.

ABSTRACT: Mitochondria are essential cellular organelles, controlling multiple signalling pathways critical for cell survival and cell death. Increasing evidence suggests that mitochondrial metabolism and functions are indispensable in tumorigenesis and cancer progression, rendering mitochondria and mitochondrial functions as plausible targets for anti-cancer therapeutics. In this review, we summarised the major strategies of selective targeting of mitochondria and their functions to combat cancer, including targeting mitochondrial metabolism, the electron transport chain and tricarboxylic acid cycle, mitochondrial redox signalling pathways, and ROS homeostasis. We highlight that delivering anti-cancer drugs into mitochondria exhibits enormous potential for future cancer therapeutic strategies, with a great advantage of potentially overcoming drug resistance. Mitocans, exemplified by mitochondrially targeted vitamin E succinate and tamoxifen (MitoTam), selectively target cancer cell mitochondria and efficiently kill multiple types of cancer cells by disrupting mitochondrial function, with MitoTam currently undergoing a clinical trial.

SUBMITTER: Dong L

PROVIDER: S-EPMC7663685 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy.

Dong Lanfeng L Gopalan Vinod V Holland Olivia O Neuzil Jiri J

International journal of molecular sciences 20201026 21

Mitochondria are essential cellular organelles, controlling multiple signalling pathways critical for cell survival and cell death. Increasing evidence suggests that mitochondrial metabolism and functions are indispensable in tumorigenesis and cancer progression, rendering mitochondria and mitochondrial functions as plausible targets for anti-cancer therapeutics. In this review, we summarised the major strategies of selective targeting of mitochondria and their functions to combat cancer, includ ...[more]

PMID: 33114695

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Project description:Simple Summary The tumor microenvironment encompasses the cellular and extracellular matrix components that support and shape the three-dimensional framework in which solid tumors develop and grow. The extracellular matrix of the tumor is characterized by increased deposition and aberrant architecture of collagen fibers. Therefore, as a key mechanical component of the tumor microenvironment, collagen plays a critical role in cancer progression, metastasis, and therapeutic response. To boost the efficacy of current anticancer therapies, including immunotherapy, innovative approaches should take into account strategies directed against the dysregulated non-cancer cell stromal components. In the current review, we provide an overview of the principal approaches to target tumor collagen to provide therapeutic benefits. Abstract The tumor stroma, which comprises stromal cells and non-cellular elements, is a critical component of the tumor microenvironment (TME). The dynamic interactions between the tumor cells and the stroma may promote tumor progression and metastasis and dictate resistance to established cancer therapies. Therefore, novel antitumor approaches should combine anticancer and anti-stroma strategies targeting dysregulated tumor extracellular matrix (ECM). ECM remodeling is a hallmark of solid tumors, leading to extensive biochemical and biomechanical changes, affecting cell signaling and tumor tissue three-dimensional architecture. Increased deposition of fibrillar collagen is the most distinctive alteration of the tumor ECM. Consequently, several anticancer therapeutic strategies have been developed to reduce excessive tumor collagen deposition. Herein, we provide an overview of the current advances and challenges of the main approaches aiming at tumor collagen normalization, which include targeted anticancer drug delivery, promotion of degradation, modulation of structure and biosynthesis of collagen, and targeting cancer-associated fibroblasts, which are the major extracellular matrix producers.

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Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy.

Publications

Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy.

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