Cracking the Code: Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review DOI Open Access

Birandra K. Sinha

Опубликована: Дек. 18, 2023

In recent years, the emergence of cancer drug resistance is one crucial tumor hallmarks which supported by level genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression ABC transporters stemness are among several key contributing molecular response mechanisms. Topo-active drugs, e.g., doxorubicin topotecan, clinically active utilized extensively against a wide variety human tumors often results in development failure to therapy. Thus, there an urgent need for incremental comprehensive understanding mechanisms specifically context topo-active drugs. This review delves into intricate mechanistic aspects these intracellular extracellular explores use potential combinatorial approaches utilizing various drugs inhibitors pathways involved resistance. We believe that this will help guide basic scientists, pre-clinicians, clinicians, policymakers toward holistic interdisciplinary strategies transcend resistance, renewing optimism ongoing battle cancer.

Язык: Английский

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review DOI Open Access
Nilesh Kumar Sharma, Anjali Bahot,

Gopinath Sekar

и другие.

Cancers, Год журнала: 2024, Номер 16(4), С. 680 - 680

Опубликована: Фев. 6, 2024

In recent years, the emergence of cancer drug resistance has been one crucial tumor hallmarks that are supported by level genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression ABC transporters, stemness among several key contributing molecular response mechanisms. Topo-active drugs, e.g., doxorubicin topotecan, clinically active utilized extensively against a wide variety human tumors often result in development failure to therapy. Thus, there is an urgent need for incremental comprehensive understanding mechanisms specifically context topo-active drugs. This review delves into intricate mechanistic aspects these intracellular extracellular explores use potential combinatorial approaches utilizing various drugs inhibitors pathways involved resistance. We believe this will help guide basic scientists, pre-clinicians, clinicians, policymakers toward holistic interdisciplinary strategies transcend resistance, renewing optimism ongoing battle cancer.

Язык: Английский

Процитировано

15
Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors DOI Creative Commons

Carolina Punziano,

Silvia Trombetti, Elena Cesaro

и другие.

Antioxidants, Год журнала: 2024, Номер 13(3), С. 298 - 298

Опубликована: Фев. 28, 2024

Ferroptosis is a type of programmed cell death that differs from apoptosis, autophagy, and necrosis related to several physio-pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, ischemia–reperfusion injuries. linked iron accumulation, eliciting dysfunction antioxidant systems, which favor the production lipid peroxides, membrane damage, ultimately, death. Thus, signaling pathways evoking ferroptosis are strongly associated with those protecting cells against excess and/or lipid-derived ROS. Here, we discuss interaction between metabolic particular focus on transcription factors implicated in regulation ferroptosis, either as triggers peroxidation or defense pathways.

Язык: Английский

Процитировано

15
Ferroptosis and cuproptosis: Metal-dependent cell death pathways activated in response to classical chemotherapy – Significance for cancer treatment? DOI Creative Commons
Mateusz Kciuk, Adrianna Gielecińska, Żaneta Kałuzińska‐Kołat

и другие.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1879(4), С. 189124 - 189124

Опубликована: Май 25, 2024

Apoptosis has traditionally been regarded as the desired cell death pathway activated by chemotherapeutic drugs due to its controlled and non-inflammatory nature. However, recent discoveries of alternative pathways have paved way for immune-stimulatory treatment approaches in cancer. Ferroptosis (dependent on iron) cuproptosis copper) hold promise selective cancer targeting overcoming drug resistance. Copper ionophores iron-bearing nano-drugs show potential clinical therapy single agents adjuvant treatments. Here we review up-to-date evidence involvement metal ion-dependent cytotoxicity classical (alkylating agents, topoisomerase inhibitors, antimetabolites, mitotic spindle inhibitors) their combinations with ferroptosis inducers, indicating prospects, advantages, obstacles use.

Язык: Английский

Процитировано

8
Ferroptosis as a promising targeted therapy for triple negative breast cancer DOI

Kasra Mokhtarpour,

Sepideh Razi,

Nima Rezaei

и другие.

Breast Cancer Research and Treatment, Год журнала: 2024, Номер 207(3), С. 497 - 513

Опубликована: Июнь 14, 2024

Язык: Английский

Процитировано

7
The crystal structure of human ferroptosis suppressive protein 1 in complex with flavin adenine dinucleotide and nicotinamide adenine nucleotide DOI Creative Commons
Shijian Feng,

Xiaofang Huang,

Dan Tang

и другие.

MedComm, Год журнала: 2024, Номер 5(3)

Опубликована: Фев. 26, 2024

Ferroptosis is a recently discovered form of regulated cell death characterized by its distinct dependence on iron and the peroxidation lipids within cellular membranes. plays crucial role in physiological pathological situations has attracted attention numerous scientists. suppressive protein 1 (FSP1) one main regulators that negatively regulates ferroptosis through GPX4-independent FSP1-CoQ10-NAD(P)H axis potential therapeutic target for ferroptosis-related diseases. However, crystal structure FSP1 not been resolved, which hinders development strategies targeting FSP1. To unravel this puzzle, we purified human (hFSP1) using baculovirus eukaryotic expression system solved at resolution 1.75 Å. Furthermore, evaluated oxidoreductase activity hFSP1 with NADH as substrate identified E156 key amino acid maintaining activity. Interestingly, our results indicated exists functions monomeric state. Mutagenesis analysis revealed critical C-terminal domain binding substrate. These findings significantly enhance understanding functional mechanism provide precise model further drug development.

Язык: Английский

Процитировано

5
Inhibition of FSP1: A new strategy for the treatment of tumors (Review) DOI

Qiangfang Dai,

Xiaoli Wei, Jumei Zhao

и другие.

Oncology Reports, Год журнала: 2024, Номер 52(2)

Опубликована: Июнь 27, 2024

Язык: Английский

Процитировано

4
Bee Pollen Potential to Modulate Ferroptosis: Phytochemical Insights for Age-Related Diseases DOI Creative Commons

Rachid Kacemi,

María G. Campos

Antioxidants, Год журнала: 2025, Номер 14(3), С. 265 - 265

Опубликована: Фев. 25, 2025

Bee pollen (BP) is one of the richest known natural resources micronutrients and bioactive phytochemicals. Some captivating bioactivities BP compounds, although being largely investigated for latter as individual molecules, remain very scarcely or completely uninvestigated in bee a whole product. Among most intriguing these bioactivities, we identified ferroptosis major one. Ferroptosis, recently discovered form cell death (connecting oxidative stress inflammation), complex pathophysiological process crucial perplexing events current challenging human diseases such cancer, neurodegeneration, general aging diseases. Many compounds were found to intricately modulate depending on cellular context by inducing this mechanism malignant cells preventing it non-malignant cells. Since research both fields, i.e., ferroptosis, still recent, deemed necessary undertake review figure out extent potential modulating mechanisms. Our proved that wide range (polyphenols, phenolamides, carotenoids, vitamins, minerals, others) substantially diverse Accordingly, phytochemicals nutrients showed interesting preclinical studies lead ferroptosis-mediated outcomes important processes, including many aging-related disorders. One paramount challenges be resolved determine how different act biological contexts, either through synergistic antagonistic behaviors. We hope our work constitutes valuable incentive future investigations promising relevant avenue.

Язык: Английский

Процитировано

0
Epithelial-mesenchymal Transition Promotes Metabolic Reprogramming to Suppress Ferroptosis DOI
Wenzheng Guo, Zhibing Duan, Jingjing Wu

и другие.

Seminars in Cancer Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Establishment of panapoptotic gene signatures of platinum-chemotherapy to predict the response of chemotherapeutic drug resistance in gastric cancer DOI Creative Commons

B. Xu,

Hailong Li, Chun‐Ting Yang

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Abstract Purpose Gastric cancer (GC) remains a daunting problem because of its inherent resistance to chemotherapy, particularly platinum-based medicines. This work was undertaken discover the molecular foundations involvement PANoptosis-related genes (PANRGs) in platinum-chemotherapy for GC. Methods A comprehensive bioinformatics analysis GC conducted dataset GSE66229 from Tumor Cancer Genome Atlas (TCGA). The RNA sequencing data were normalized, and differential expression performed identify PANRGs that distinguish platinum-sensitive from-resistant Subsequent GO functional KEGG pathway analyses elucidate biological relevance these genes. Furthermore, prognostic model constructed predict survival outcomes patients utilizing identified PANRGs. Chemotherapeutic drug sensitivity using Drug Sensitivity Genomics (GDSC) database. Results yielded 18 significantly differentially expressed platinum-resistant comparing GC, which includes upregulated genes, CASP9, CHMP6, BAG3, EYA2, HSPB1, SHH, SLC9A3R1, SMAD3, FTH1, downregulated TP53, ADORA1, CAAP1, CHEK2, DAP3, INHBA, URI1, YWHAH, XIAP. These enriched processes pathways associated with cell cycle, apoptosis, platinum resistance. Based on expressions DAP3 XIAP single factor analysis, accurately stratified into high- low-risk groups, distinct differences identified. verified an independent GEO dataset, demonstrating resilience generalizability. AZD6738, Dihydrorotenone, Paclitaxel, MK-1775, Osimertinib, Ulixertinib, AZD2014, Cytarabine, PD0325901, Wee1 inhibitors top ten chemotherapeutic medicines (comparison IC50 between P < 0.05). Conclusion finding underscores pivotal role PANoptosis modulating evaluated as models.

Язык: Английский

Процитировано

0
Oxidative Stress: A New Pathophysiological Pathway in Parkinson’s Disease and a Potential Target of the Brain‐Sport Crosstalk DOI Creative Commons
Stefano Caproni, Alessio Di Fonzo, Carlo Colosimo

и другие.

Parkinson s Disease, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Oxidative stress (OS), a condition that occurs when the balance between reactive oxygen species production and antioxidant defense mechanisms is disrupted, has been implicated in pathogenesis of several neurological conditions, including neurodegenerative vascular disorders. Ferroptosis mechanism mediating OS-induced damage, with growing evidence specific involvement both Parkinson's disease (PD) ischemic stroke. Regular physical activity may have an effect by increasing nonenzymatic enzymatic antioxidants. Among biological mediators activity, irisin act as agent capable inducing systemic changes crossing brain-blood barrier. This review aims to describe main role OS pathophysiology PD, highlighting putative emphasizing potential targeting possible shared preventive symptomatic treatment approach.

Язык: Английский

Процитировано

0