Targeting autophagy is a promising therapeutic strategy to overcome chemoresistance and reduce metastasis in osteosarcoma

Liao, Yuxin; Yu, Haiyang; Lv, Jiyang; Cai, Yan‐Rong; Liu, Fei; He, Zhimin; He, Shi‐Sheng

doi:10.3892/ijo.2019.4902

Cited by 34 publications

(45 citation statements)

References 77 publications

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“…The elimination and recycling of damaged proteins and organelles are driven by autophagy, which provides energy to the cells. Autophagy can be activated by chemotherapy and can promote increased chemosensitivity, as well as drug resistance in OS (Camuzard et al , 2019; Liao et al , 2019). Thus, drugs regulating autophagy may be an option to overcome drug resistance in the future.…”

Section: Epidemiology Of Sarcomamentioning

confidence: 99%

Sarcoma treatment in the era of molecular medicine

et al. 2020

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Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult‐to‐treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.

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Section: Epidemiology Of Sarcomamentioning

confidence: 99%

Sarcoma treatment in the era of molecular medicine

et al. 2020

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“…Chloroquine and hydroxychloroquine are the only autophagy inhibitors approved by the FDA for clinical use (178), comprehensive reviews are examining the role of various compounds and biological molecules in the regulation of autophagy and various ATG genes (160,176,(179)(180)(181). Clinical trials are underway in which inhibitors of autophagy are administered in combination with chemotherapy or targeted therapy (182,183).…”

Section: Role Of Autophagy In Chemotherapy and Target Therapy Resistancementioning

confidence: 99%

The Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-tumor Activity

et al. 2020

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During tumorigenesis, cancer cells are exposed to a wide variety of intrinsic and extrinsic stresses that challenge homeostasis and growth. Cancer cells display activation of distinct mechanisms for adaptation and growth even in the presence of stress. Autophagy is a catabolic mechanism that aides in the degradation of damaged intracellular material and metabolite recycling. This activity helps meet metabolic needs during nutrient deprivation, genotoxic stress, growth factor withdrawal and hypoxia. However, autophagy plays a paradoxical role in tumorigenesis, depending on the stage of tumor development. Early in tumorigenesis, autophagy is a tumor suppressor via degradation of potentially oncogenic molecules. However, in advanced stages, autophagy promotes the survival of tumor cells by ameliorating stress in the microenvironment. These roles of autophagy are intricate due to their interconnection with other distinct cellular pathways. In this review, we present a broad view of the participation of autophagy in distinct phases of tumor development. Moreover, autophagy participation in important cellular processes such as cell death, metabolic reprogramming, metastasis, immune evasion and treatment resistance that all contribute to tumor development, is reviewed. Finally, the contribution of the hypoxic and nutrient deficient tumor microenvironment in regulation of autophagy and these hallmarks for the development of more aggressive tumors is discussed.

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“…Some authors have actually observed that the depletion of autophagy decreased the viability of chronic myeloid leukemia CD34+ progenitor cells, whereas its inhibition in hematopoietic stem cells (HSC) has favored the development of hematopoietic diseases (Auberger and Puissant, 2017;Levine and Kroemer, 2019). On the other hand, after treatment with synthetic or natural compounds, there are some evidences that when the autophagosomal/lysosomal pathway is over activated for a prolonged time the autophagic cell death (ACD, type II cell death) can occur (Liao et al, 2019;Linder and Kögel, 2019). Arsenic trioxide (ATO) has been proved to induce ACD in several cancer cells.…”

Section: Autophagy In Cancermentioning

confidence: 99%

The Exploitation of Liposomes in the Inhibition of Autophagy to Defeat Drug Resistance

Condello¹,

Mancini

Meschini³

2020

Front. Pharmacol.

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Autophagy is a mechanism involved in many human diseases and in cancers can have a cytotoxic/cytostatic or protective action, being in the latter case involved in multidrug resistance. Understanding which of these roles autophagy has in cancer is thus fundamental for therapeutical decisions because it permits to optimize the therapeutical approach by activating or inhibiting autophagy according to the progression of the disease. However, a serious drawback of cancer treatment is often the scarce availability of drugs and autophagy modulators at the sites of interest. In the recent years, several nanocarriers have been developed and investigated to improve the solubility, bioavailability, controlled release of therapeutics and increase their cytotoxic effect on cancer cell. Here we have reviewed only liposomes as carriers of chemotherapeutics and autophagy inhibitors because they have low toxicity and immunogenicity and they are biodegradable and versatile. In this review after the analysis of the dual role of autophagy, of the main autophagic pathways, and of the role of autophagy in multidrug resistance, we will focus on the most effective liposomal formulations, thus highlighting the great potential of these targeting systems to defeat cancer diseases.

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Targeting autophagy is a promising therapeutic strategy to overcome chemoresistance and reduce metastasis in osteosarcoma

Cited by 34 publications

References 77 publications

Sarcoma treatment in the era of molecular medicine

Sarcoma treatment in the era of molecular medicine

The Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-tumor Activity

The Exploitation of Liposomes in the Inhibition of Autophagy to Defeat Drug Resistance

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