Metabolic Remodelling: An Accomplice for New Therapeutic Strategies to Fight Lung Cancer

Mendes, Cindy; Serpa, Jacinta

doi:10.3390/antiox8120603

Cited by 15 publications

(17 citation statements)

References 222 publications

(312 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chemoresistant cancer cells become highly adapted to intrinsic or drug-induced oxitive stress by upregulating their antioxidant systems [ 22 , 23 ] ( Figure 2 ). In a recent review, Sferrazzo et al reported that HO-1 overexpression is involved in chemotherapy and radiotherapy resistance of brain tumors such as neuroblastoma, medulloblastoma, meningioma, and astrocytoma [ 24 ].…”

Section: Oxidative Stress and Chemoresistancementioning

confidence: 99%

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

et al. 2021

View full text Add to dashboard Cite

Chemoresistance represents the main obstacle to cancer treatment with both conventional and targeted therapy. Beyond specific molecular alterations, which can lead to targeted therapy, metabolic remodeling, including the control of redox status, plays an important role in cancer cell survival following therapy. Although cancer cells generally have a high basal reactive oxygen species (ROS) level, which makes them more susceptible than normal cells to a further increase of ROS, chemoresistant cancer cells become highly adapted to intrinsic or drug-induced oxidative stress by upregulating their antioxidant systems. The antioxidant response is principally mediated by the transcription factor Nrf2, which has been considered the master regulator of antioxidant and cytoprotective genes. Nrf2 expression is often increased in several types of chemoresistant cancer cells, and its expression is mediated by diverse mechanisms. In addition to Nrf2, other transcription factors and transcriptional coactivators can participate to maintain the high antioxidant levels in chemo and radio-resistant cancer cells. The control of expression and function of these molecules has been recently deepened to identify which of these could be used as a new therapeutic target in the treatment of tumors resistant to conventional therapy. In this review, we report the more recent advances in the study of Nrf2 regulation in chemoresistant cancers and the role played by other transcription factors and transcriptional coactivators in the control of antioxidant responses in chemoresistant cancer cells.

show abstract

Section: Oxidative Stress and Chemoresistancementioning

confidence: 99%

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

et al. 2021

View full text Add to dashboard Cite

show abstract

“…These changes allow them to meet the requirements of the rapid cell division and to avoid signals that would lead to their growth arrest and execution, such as apoptotic signals [7,9,10]. Among the metabolic alterations observed in lung cancer, those associated with lipid metabolism have recently received increasing attention and recognition [11]. In this review, we explored the role of lipid metabolic rewiring in lung cancer development and progression and in resistance to therapies, focusing in particular on its connection with EGFR signaling.…”

Section: Introductionmentioning

confidence: 99%

Reprogramming of Lipid Metabolism in Lung Cancer: An Overview with Focus on EGFR-Mutated Non-Small Cell Lung Cancer

Eltayeb

Monica

Tiseo

et al. 2022

Cells

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer deaths worldwide. Most of lung cancer cases are classified as non-small cell lung cancers (NSCLC). EGFR has become an important therapeutic target for the treatment of NSCLC patients, and inhibitors targeting the kinase domain of EGFR are currently used in clinical settings. Recently, an increasing interest has emerged toward understanding the mechanisms and biological consequences associated with lipid reprogramming in cancer. Increased uptake, synthesis, oxidation, or storage of lipids has been demonstrated to contribute to the growth of many types of cancer, including lung cancer. In this review, we provide an overview of metabolism in cancer and then explore in more detail the role of lipid metabolic reprogramming in lung cancer development and progression and in resistance to therapies, emphasizing its connection with EGFR signaling. In addition, we summarize the potential therapeutic approaches targeting lipid metabolism for lung cancer treatment.

show abstract

“…Cellular stress responses are bioenergetically demanding as a suite of stress proteins need to be synthesized de nova in large quantities [26][27][28][29][30][31] . As a result, cells may enter a survival mode where they undergo global translational and metabolic reprogramming to preserve and divert energy for the stress response while specialized cell functions may be compromised 32,33 . Therefore, the onset of adaptive transcriptional stress control, for the purpose of cell survival, may be regarded as the onset of functional adversity.…”

Section: Introductionmentioning

confidence: 99%

The phosphoproteome is a first responder in tiered cellular adaptation to chemical stress followed by proteomics and transcriptomics alteration

Chen

et al. 2022

Preprint

View full text Add to dashboard Cite

Next-generation risk assessment for environmental chemicals and ingredients in consumer products involves a weight of evidence (WoE) framework integrating a suite of new approach methodologies (NAMs) based on points of departure (PoD) obtained from in vitro assays. Omics techniques provide broad coverages of the molecular toxicity pathway space. Transcriptomics assays especially play a leading role by providing relatively conservative PoDs in comparison with apical endpoints. However, it is unclear whether and how parameters measured using other omics technicquesparticipate in the cellular response to chemical perturbations, especially at exposure levels below the transcriptomically defined PoD. Multi-omics coverage may provide additional sensitive or confirmative biomarkers to complement and reduce the uncertainty in safety decisions made using targeted and transcriptomics assays. In the present study, we compared changes in transcriptomics, proteomics and phosphoproteomics with two prototype compounds, coumarin, as a main study and doxorubicin, as a complementary study to understand the sensitivity of the three omics techniques in response to chemically-induced changes in HepG2 and AC16 cells. With measurements obtained for multiple chemical concentrations and time points, we demonstrated that, compared with proteomics and transcriptomics, phosphoproteomics alterations occur not only earlier in time as expected, but also at much lower chemical concentrations and hence are proximal to the very early effects induced by chemical exposure. The phosphoproteomics changes appear to approach maximum when the transcriptomics alterations begin to be initiated. The results are consistent with a tiered framework of cellular response to chemical insults, where posttranslational modification of preexisting proteins is first seen before transcriptomics induction is engaged to launch a more energy-expensive defense that defines a useful PoD. We conclude that as the cost becomes more affordable, proteomics covering posttranslational modifications can be utilized to provide a more complete coverage of chemical-induced cellular alteration and supplement transcriptomics-based health safety decision making.

show abstract

Metabolic Remodelling: An Accomplice for New Therapeutic Strategies to Fight Lung Cancer

Cited by 15 publications

References 222 publications

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

Reprogramming of Lipid Metabolism in Lung Cancer: An Overview with Focus on EGFR-Mutated Non-Small Cell Lung Cancer

The phosphoproteome is a first responder in tiered cellular adaptation to chemical stress followed by proteomics and transcriptomics alteration

Contact Info

Product

Resources

About