Autophagy Contributes to Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Tumors

Reyes-Castellanos, Gabriela; Hadi, Nadine Abdel; Carrier, Alice

doi:10.3390/cells11030426

Cited by 20 publications

(15 citation statements)

References 124 publications

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“…Therefore, autophagy is of particular importance for cancers, such as pancreatic ductal adenocarcinoma. Reyes-Castellanos G ( 101 ) proposed that high autophagic activity in pancreatic ductal adenocarcinoma is markedly related to resistance to current therapies. The inhibitions in the last stage of autophagy can overcome drug resistance, such as chloroquine and its derivative hydroxychloroquine ( 102 ).…”

Section: Resultsmentioning

confidence: 99%

Trends in metabolic signaling pathways of tumor drug resistance: A scientometric analysis

et al. 2022

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BackgroundCancer chemotherapy resistance is one of the most critical obstacles in cancer therapy. Since Warburg O first observed alterations in cancer metabolism in the 1950s, people gradually found tumor metabolism pathways play a fundamental role in regulating the response to chemotherapeutic drugs, and the attempts of targeting tumor energetics have shown promising preclinical outcomes in recent years. This study aimed to summarize the knowledge structure and identify emerging trends and potential hotspots in metabolic signaling pathways of tumor drug resistance research.MethodsPublications related to metabolic signaling pathways of tumor drug resistance published from 1992 to 2022 were retrieved from the Web of Science Core Collection database. The document type was set to articles or reviews with language restriction to English. Two different scientometric software including Citespace and VOS viewer were used to conduct this scientometric analysis.ResultsA total of 2,537 publications including 1,704 articles and 833 reviews were retrieved in the final analysis. The USA made the most contributions to this field. The leading institution was the University of Texas MD Anderson Cancer Center. Avan A was the most productive author, and Hanahan D was the key researcher with the most co-citations, but there is no leader in this field yet. Cancers was the most influential academic journal, and Oncology was the most popular research field. Based on keywords occurrence analysis, these selected keywords could be roughly divided into five main topics: cluster 1 (study of cancer cell apoptosis pathway); cluster 2 (study of resistance mechanisms of different cancer types); cluster 3 (study of cancer stem cells); cluster 4 (study of tumor oxidative stress and inflammation signaling pathways); and cluster 5 (study of autophagy). The keywords burst detection identified several keywords as new research hotspots, including “tumor microenvironment,” “invasion,” and “target”.ConclusionTumor metabolic reprogramming of drug resistance research is advancing rapidly. This study serves as a starting point, providing a thorough overview, the development landscape, and future opportunities in this field.

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Section: Resultsmentioning

confidence: 99%

Trends in metabolic signaling pathways of tumor drug resistance: A scientometric analysis

et al. 2022

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“…Genetically engineered PDAC mice missing the important autophagy genes Atg5 or Atg7 form low-grade premalignant pancreatic lesions, indicating that autophagy continues to play a defensive function in the initial stages of tumorigenesis [ 15 ]. However, autophagy speeds up tumor initiation rather than preventing tumor formation in a mouse model with carcinogenic KRAS and homozygous deletion of P53 , with tumor proliferation enhanced by greater glucose ingestion [ 58 ].…”

Section: Interactions For Both Autophagy and Pdacmentioning

confidence: 99%

“…Autophagy can selectively and precisely target multiple cell compartments almost simultaneously, including mitochondria, endoplasmic reticulum, peroxisomes, nucleus, lysosomes, and even other cellular organelles such as fat droplets and accumulates, to maintain cell stability under both normal and abnormal conditions [ 13 , 14 ]. Many studies have individually examined macroautophagy, targeted autophagy, and autophagy regulators to broaden our knowledge of how autophagy functions in PC [ 15 , 16 ]. This review focuses on the role of autophagy in PC tumor formation, aggressiveness, and medicinal weaknesses.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

et al. 2022

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Pancreatic cancer (PC) begins within the organ of the pancreas, which produces digestive enzymes, and is one of the formidable cancers for which appropriate treatment strategies are urgently needed. Autophagy occurs in the many chambers of PC tissue, including cancer cells, cancer-related fibroblasts, and immune cells, and can be fine-tuned by various promotive and suppressive signals. Consequently, the impacts of autophagy on pancreatic carcinogenesis and progression depend greatly on its stage and conditions. Autophagy inhibits the progress of preneoplastic damage during the initial phase. However, autophagy encourages tumor formation during the development phase. Several studies have reported that both a tumor-promoting and a tumor-suppressing function of autophagy in cancer that is likely cell-type dependent. However, autophagy is dispensable for pancreatic ductal adenocarcinoma (PDAC) growth, and clinical trials with autophagy inhibitors, either alone or in combination with other therapies, have had limited success. Autophagy’s dual mode of action makes it therapeutically challenging despite autophagy inhibitors providing increased longevity in medical studies, highlighting the need for a more rigorous review of current findings and more precise targeting strategies. Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC.

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“…Metabolic niches also contribute significantly to cancer development and progression. Autophagy plays a pivotal role in supporting the growth of PDAC through fibroblasts [ 84 ]. Autophagy allows fibroblasts to break down misfolded proteins and ECM, releasing large quantities of amino acids into the microenvironment [ 85 ].…”

Section: Metabolic Reprogramming Of the Main Energy Pathways In Pdacmentioning

confidence: 99%

Metabolic Pathways as a Novel Landscape in Pancreatic Ductal Adenocarcinoma

Ali

Chianese

Papulino

et al. 2022

Cancers

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Metabolism plays a fundamental role in both human physiology and pathology, including pancreatic ductal adenocarcinoma (PDAC) and other tumors. Anabolic and catabolic processes do not only have energetic implications but are tightly associated with other cellular activities, such as DNA duplication, redox reactions, and cell homeostasis. PDAC displays a marked metabolic phenotype and the observed reduction in tumor growth induced by calorie restriction with in vivo models supports the crucial role of metabolism in this cancer type. The aggressiveness of PDAC might, therefore, be reduced by interventions on bioenergetic circuits. In this review, we describe the main metabolic mechanisms involved in PDAC growth and the biological features that may favor its onset and progression within an immunometabolic context. We also discuss the need to bridge the gap between basic research and clinical practice in order to offer alternative therapeutic approaches for PDAC patients in the more immediate future.

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Autophagy Contributes to Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Tumors

Cited by 20 publications

References 124 publications

Trends in metabolic signaling pathways of tumor drug resistance: A scientometric analysis

Trends in metabolic signaling pathways of tumor drug resistance: A scientometric analysis

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

Metabolic Pathways as a Novel Landscape in Pancreatic Ductal Adenocarcinoma

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