Therapeutic implications of autophagy in cancer treatment (original) (raw)
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Therapeutic implications of autophagy in cancer treatment Arabian Journal of Medical Sciences
Article Info Autophagy is a survival process in which a cell preserves its components in case of nutrient deprivation by recycling its digested contents and cannibalizing itself. It is characterized by formation of double membrane autophagosomes and it has a role in cancer treatment by many mechanisms. Interestingly, autophagy has a significant effect in the treatment of many diseases by different mechanisms. Autophagy has been included as a treatment mechanism of various diseases, such as degenerative diseases of the muscle and nervous system. Abundant autophagic vacuoles were formed inside the damaged cells in many of these degenerative disorders. Autophagy can help both living cells and cancer cells to survive so some antitumor agents targeted autophagy in cancer cells. In this review, we illustrated the definition of autophagy, autophagic pathways, therapeutic implications of autophagy in cancer, the relationship between autophagy and cell death, inflammation, and necrosis.
Autophagy and Cancer Treatment Review
2021
Autophagy is a catabolic process that targets impaired organelles and proteins for lysosomal degradation to maintain cell hemostasis. Autophagy in cancer is dynamic and, more specifically, depending on the stage and type of tumor. Researches in genetically engineered mouse models are agreed with the concept that autophagy can constrain initiation of the tumor by controlling oxidative stress and DNA damage, while in established tumors, autophagy can also be required for tumor survival. As shown in preclinical models, suppression of autophagy restored chemotherapy sensitivity against tumor cells. Targeting autophagy in cancer will develop a new era for anti-cancer drugs, but more specific and potent inhibitors of autophagy are needed. The role of autophagy in cancer cells continues to emerge, and further studying to identify optimum strategies to modulate autophagy for therapeutic advantage.
Challenges and Therapeutic Opportunities of Autophagy in Cancer Therapy
Cancers
Autophagy is a physiological cellular process that is crucial for development and can occurs in response to nutrient deprivation or metabolic disorders. Interestingly, autophagy plays a dual role in cancer cells—while in some situations, it has a cytoprotective effect that causes chemotherapy resistance, in others, it has a cytotoxic effect in which some compounds induce autophagy-mediated cell death. In this review, we summarize strategies aimed at autophagy for the treatment of cancer, including studies of drugs that can modulate autophagy-mediated resistance, and/or drugs that cause autophagy-mediated cancer cell death. In addition, the role of autophagy in the biology of cancer stem cells has also been discussed.
The Role of Autophagy in Cancer: Therapeutic Implications
Molecular Cancer Therapeutics, 2011
Autophagy is a homeostatic, catabolic degradation process whereby cellular proteins and organelles are engulfed into autophagosomes, digested in lysosomes and recycled to sustain cellular metabolism. Autophagy has dual roles in cancer, acting as both a tumor suppressor by preventing the accumulation of damaged proteins and organelles and as a mechanism of cell survival that can promote the growth of established tumors. Tumor cells activate autophagy in response to cellular stress including hypoxia and increased metabolic demands related to rapid cell proliferation. Autophagy-related stress tolerance can enable cell survival by maintaining energy production that can lead to tumor growth and therapeutic resistance, as shown in preclinical models where the inhibition of autophagy can restore chemosensitivity and enhance tumor cell death. These results established autophagy as a therapeutic target and have led to multiple early phase clinical trials in humans evaluating autophagy inhibition using hydroxychloroquine in combination with chemotherapy or targeted agents. Targeting autophagy in cancer provides new opportunities for drug development since more potent and specific inhibitors of autophagy are needed. The role of autophagy and its regulation in cancer cells continues to emerge and studies aim to define optimal strategies to modulate autophagy for therapeutic advantage.
Therapeutic Implications of Autophagy
American Journal of PharmTech Research, 2018
Autophagy is an intracellular has demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles, which are sometimes complex. Autophagy consists of several sequential steps sequestration, transport to lysosomes, degradation, and utilization of degradation products and each step may exert different function. In this review, the process of autophagy is summarized, and the role of autophagy is discussed in various diseases like Cancer, Neurodegenerative disease etc.
F1000Prime Reports, 2015
Autophagy is a catabolic degradation process in which cellular proteins and organelles are engulfed by double-membrane autophagosomes and degraded in lysosomes. Autophagy has emerged as a critical pathway in tumor development and cancer therapy, although its precise function remains a conundrum. The current consensus is that autophagy has a dual role in cancer. On the one hand, autophagy functions as a tumor suppressor mechanism by preventing the accumulation of damaged organelles and aggregated proteins. On the other hand, autophagy is a key cell survival mechanism for established tumors; therefore autophagy inhibition suppresses tumor progression. Here, we summarize recent progress on the role of autophagy in tumorigenesis and cancer therapy.
An overview on the role of autophagy in cancer therapy
Hematology & Medical Oncology, 2017
Autophagy is a highly regulated catabolic process through which cells recycle their own constituents by delivering them into lysosomes. Several studies have demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles in cells. In cancer, autophagy has been described to have paradoxical roles, acting both as tumor suppressor and as tumor promoter. In particular, it may exert different functions in response to cancer therapy, causing cancer resistance or increasing sensitivity to chemotherapeutic drugs and radiation. Therefore, autophagy could provide new means for the enhancement of antitumor drugs and radiation effectiveness.
Pharmacological inhibitors of autophagy as novel cancer therapeutic agents
Pharmacological research, 2016
Autophagy is an evolutionarily conserved cellular degradative process in which intracellular components (cellular proteins and organelles) are engulfed in autophagosomes which then fuse with lysosomes to form autolysosome for degradation. Autophagy is closely implicated in various physio-pathological processes and human diseases. Among them, the roles of autophagy in cancer have been extensively studied. Increasing evidence has demonstrated that inhibiting autophagy is a novel and promising approach in cancer therapy, based on the notion that autophagy is a pro-survival mechanism in cancer cells under therapeutic stress, and induction of autophagy is associated with chemoresistance of cancer cells to chemotherapeutic agents. Thus, suppression of autophagy would sensitize resistance tumor cells to cancer therapeutic agents, thereby supporting the clinical application of autophagy inhibitors. In recent years, significant progress has been achieved in developing autophagy inhibitors an...
TURKISH JOURNAL OF BIOLOGY, 2014
Introduction Autophagy is a basic cellular event conserved in all eukaryotes from yeast to man. It serves as an intracellular quality-control mechanism recycling long-lived or misfolded/aggregate-prone proteins and damaged organelles, such as mitochondria. Moreover, under stress conditions, autophagy is upregulated in order to generate building blocks that are necessary for cellular survival (Kuma and Mizushima, 2010; Rabinowitz and White, 2010). Therefore, autophagy mainly serves as a stress-adaptation and survival mechanism (Su et al., 2013). However, under certain conditions, autophagy was reported to contribute to programmed cell death either indirectly through crosstalk mechanisms with apoptosis (Gozuacik and Kimchi, 2004; Oral et al., 2012; Rubinstein and Kimchi, 2012) or directly through autophagic cell death (Gozuacik and Kimchi, 2007). Abnormalities of autophagy were reported in various diseases, including neurodegenerative diseases, lysosomal storage diseases, infections, metabolic diseases, and ischemia/reperfusion injury (Schneider and Cuervo, 2014). Cancer is no exception. The roles of autophagy in cancer formation, growth, ischemia resistance, metabolic changes, neovascularization, and even metastasis and tumor dormancy were reported (Gewirtz, 2009; Guo et al., 2013b; Murrow and Debnath, 2013). Moreover, autophagic capacity was shown to significantly affect responses of cancer cells to anticancer agents and radiation (Eberhart et al., 2013). In this review we will mainly focus on the role of autophagy in cancer formation and cancer therapy. 2. Basic mechanisms of autophagy There are 2 major catabolic mechanisms in mammalian cells: the ubiquitin-proteasome system and the autophagylysosomal system. Proteasomes degrade mainly shortlived and soluble proteins following their regulated ubiquitinylation (Hershko and Ciechanover, 1998). In contrast, lysosomal pathways rely on the delivery of cytosolic contents into the lumen of the organelle, an event that is followed by their degradation by specific hydrolases. Here, ingested cytoplasmic targets might be various. The list includes long-lived proteins, old and damaged organelles (e.g., mitochondria and peroxisomes); misfolded, mutant, and/or aggregated proteins; and pathogens such as bacteria, viruses, and parasites. So far, 3 subtypes of autophagy have been described in mammals: microautophagy, chaperone-mediated autophagy (CMA), and macroautophagy (Klionsky and Schulman, 2014). Microautophagy proceeds through direct invagination of the vacuolar/lysosomal membrane and engulfment of nearby cytosolic materials (Uttenweiler et al., 2005). In addition to cargo digestion, microautophagic vacuoles also contribute to the maintenance of organelle size and membrane composition (Mijaljica and Devenish, 2011).