Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 18, 2022

Drug resistance represents a major obstacle in cancer management, and the mechanisms underlying stress adaptation of cells response to therapy-induced hostile environment are largely unknown. As central organelle for cellular energy supply, mitochondria can rapidly undergo dynamic changes integrate signaling pathways provide bioenergetic biosynthetic flexibility cells, which contributes multiple aspects tumor characteristics, including drug resistance. Therefore, targeting therapy overcoming has attracted increasing attention various types cancer. Multiple mitochondrial processes, dynamics, metabolism, apoptotic regulatory machinery, have been demonstrated be potential targets. However, recent insights into revealed complexity structure functions, elusive functions biology, inaccessibility mitochondria, posed challenges clinical application mitochondrial-based therapeutic strategies. discovery both novel mitochondria-targeting agents innovative approaches is urgently required. Here, we review most literature summarize molecular their intricate connection with In addition, an overview emerging strategies target effectively chemoresistance highlighted, emphasis on repositioning delivery approaches, may accelerate compounds therapy.

Language: Английский

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Antioxidant Therapy in Cancer: Rationale and Progress

Antioxidants, Journal Year: 2022, Volume and Issue: 11(6), P. 1128 - 1128

Published: June 8, 2022

Cancer is characterized by increased oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants. Enhanced ROS accumulation, as a result of metabolic disturbances signaling aberrations, can promote carcinogenesis malignant progression inducing gene mutations activating pro-oncogenic signaling, providing possible rationale for targeting stress in cancer treatment. While numerous antioxidants have demonstrated therapeutic potential, their clinical efficacy remains unproven. Here, we review the for, recent advances in, pre-clinical research on antioxidant therapy cancer, including with nonenzymatic antioxidants, such NRF2 activators, vitamins, N-acetylcysteine GSH esters, or enzymatic NOX inhibitors SOD mimics. In addition, will offer insights into prospective options improving effectiveness therapy, which may expand its applications

Language: Английский

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Modulation of redox homeostasis: A strategy to overcome cancer drug resistance

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 22, 2023

Cancer treatment is hampered by resistance to conventional therapeutic strategies, including chemotherapy, immunotherapy, and targeted therapy. Redox homeostasis manipulation one of the most effective innovative techniques for overcoming drug resistance. Reactive oxygen species (ROS), previously considered intracellular byproducts aerobic metabolism, are now known regulate multiple signaling pathways as second messengers. cells cope with elevated amounts ROS during therapy upregulating antioxidant system, enabling tumor via a variety mechanisms. In this review, we aim shed light on redox modification that may contribute We summarized molecular mechanisms which signaling-regulated resistance, altered efflux, action targets enhanced DNA damage repair, maintained stemness, reshaped microenvironment. A comprehensive understanding these interrelationships should improve efficacy from fundamental clinical research point view.

Language: Английский

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Protein degradation: expanding the toolbox to restrain cancer drug resistance

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Jan. 24, 2023

Abstract Despite significant progress in clinical management, drug resistance remains a major obstacle. Recent research based on protein degradation to restrain has attracted wide attention, and several therapeutic strategies such as inhibition of proteasome with bortezomib proteolysis-targeting chimeric have been developed. Compared intervention at the transcriptional level, targeting process seems be more rapid direct strategy. Proteasomal proteolysis lysosomal are most critical quality control systems responsible for proteins or organelles. Although proteasomal inhibitors (e.g., chloroquine) achieved certain improvements some application scenarios, their routine practice is still long way off, which due lack precise capabilities inevitable side effects. In-depth studies regulatory mechanism regulators, including E3 ubiquitin ligases, deubiquitylating enzymes (DUBs), chaperones, expected provide clues developing reducing Here, we discuss underlying mechanisms regulating efflux, metabolism, DNA repair, target alteration, downstream bypass signaling, sustaining stemness, tumor microenvironment remodeling delineate functional roles resistance. We also highlight specific DUBs, discussing possible modulating cancer A systematic summary molecular basis by regulates will help facilitate development appropriate strategies.

Language: Английский

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Treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 71, P. 101002 - 101002

Published: Aug. 22, 2023

Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon, rectus, and prostate. For patients who lose the opportunity for radical surgery, medication available to provide potential clinical benefits. However, drug resistance big obstacle obtain desired prognosis. In this review, we summary treatment strategies mechanisms adenocarcinoma different including pancreatic cancer, gastric adenocarcinoma, colorectal lung prostate cancer. Although underlying molecular involved vary one organ other, there are several targets that universal targeting these molecules could potentially reverse adenocarcinomas.

Language: Английский

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The Cancer Antioxidant Regulation System in Therapeutic Resistance

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 778 - 778

Published: June 27, 2024

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cells adeptly maintain elevated levels both ROS and antioxidants through process termed "redox reprogramming". This balance optimizes proliferative influence while simultaneously reducing potential for cause damage cell. some cases, adapted antioxidant machinery can hamper efficacy treatments neoplastic diseases, representing significant facet resistance mechanisms observed therapy. this review, we outline contribution systems therapeutic resistance. We detail fundamental constituents these systems, encompassing central regulatory involving transcription factors (of particular importance is KEAP1/NRF2 signaling axis), molecular effectors antioxidants, auxiliary responsible NADPH generation. Furthermore, present recent clinical trials based on targeted treatment cancer, assessing as well challenges strategy Additionally, summarize pressing issues field, with aim illuminating path toward emergence novel anticancer approaches by orchestrating redox signaling.

Language: Английский

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Enhancing chemotherapy response prediction via matched colorectal tumor-organoid gene expression analysis and network-based biomarker selection

Translational Oncology, Journal Year: 2025, Volume and Issue: 52, P. 102238 - 102238

Published: Jan. 5, 2025

Language: Английский

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Recent advances in Surface-Enhanced Raman Scattering (SERS) for the diagnosis, treatment, and prognosis of ovarian cancer

Microchemical Journal, Journal Year: 2025, Volume and Issue: unknown, P. 112787 - 112787

Published: Jan. 1, 2025

Language: Английский

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Cyclophilin A/CD147 Interaction: A Promising Target for Anticancer Therapy

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9341 - 9341

Published: Aug. 19, 2022

Cyclophilin A (CypA), which has peptidyl-prolyl cis-trans isomerase (PPIase) activity, regulates multiple functions of cells by binding to its extracellular receptor CD147. The CypA/CD147 interaction plays a crucial role in the progression several diseases, including inflammatory coronavirus infection, and cancer, activating CD147-mediated intracellular downstream signaling pathways. Many studies have identified CypA CD147 as potential therapeutic targets for cancer. Their overexpression promotes growth, metastasis, resistance, stem-like properties cancer is related poor prognosis patients with This review aims understand biology roles pathology targeting axis. To validate clinical significance interaction, we analyzed expression levels PPIA BSG genes encoding CD147, respectively, wide range tumor types using Cancer Genome Atlas (TCGA) database. We observed significant association between PPIA/BSG prognosis, such low survival rate high stage, types. Furthermore, was positively correlated many cancers. Therefore, this supports hypothesis that may improve treatment outcomes

Language: Английский

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PPIH acts as a potential predictive biomarker for patients with common solid tumors

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: June 4, 2024

Abstract Background Our previous studies have indicated that mRNA and protein levels of PPIH are significantly upregulated in Hepatocellular Carcinoma (LIHC) could act as predictive biomarkers for patients with LIHC. Nonetheless, the expression implications etiology progression common solid tumors yet to be explored, including its potential a serum tumor marker. Methods We employed bioinformatics analyses, augmented clinical sample evaluations, investigate gene regulation networks various tumors. also assessed association between overall survival (OS) cancer using Kaplan-Meier analysis TCGA database information. Furthermore, we evaluated feasibility diagnostic efficacy marker by integrating serological established markers. Results Through pan-cancer analysis, found multiple were different from those normal tissues. This study is first report markedly elevated LIHC, Colon adenocarcinoma (COAD), Breast (BC), associated worse prognosis these patients. Conversely, decreased (LIHC, COAD, BC, gastric cancer), when combined traditional markers, offer enhanced sensitivity specificity diagnosis. Conclusion findings propose may serve valuable biomarker patients, secreted marker, providing insights into role development progression.

Language: Английский

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