Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 106-107, P. 123 - 142
Published: Sept. 30, 2024
Language: Английский
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)
Published: Aug. 1, 2024
Abstract Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated as natural byproducts during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in diverse functions, cell signaling and immune responses. However, a disturbance the balance between production antioxidant defenses can lead to an excessive buildup, causing oxidative stress. This stress damages essential components, lipids, proteins, DNA, potentially culminating death. form of death take various forms, such ferroptosis, apoptosis, necroptosis, pyroptosis, paraptosis, parthanatos, oxeiptosis, each displaying distinct genetic, biochemical, characteristics. The investigation holds promise for development pharmacological agents that used prevent tumorigenesis or treat established cancer. Specifically, targeting key SLC7A11, GCLC, GPX4, TXN, TXNRD, represents emerging approach inducing cancer cells. review provides comprehensive summary recent progress, opportunities, challenges therapy.
Language: Английский
Citations
64
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: June 6, 2024
Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.
Language: Английский
Citations
51
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: May 18, 2024
Abstract Aging and cancer exhibit apparent links that we will examine in this review. The null hypothesis aging coincide because both are driven by time, irrespective of the precise causes, can be confronted with idea share common mechanistic grounds referred to as ‘hallmarks’. Indeed, several hallmarks also contribute carcinogenesis tumor progression, but some molecular cellular characteristics may reduce probability developing lethal cancer, perhaps explaining why very old age (> 90 years) is accompanied a reduced incidence neoplastic diseases. We discuss possibility process itself causes meaning time-dependent degradation supracellular functions accompanies produces byproduct or ‘age-associated disease’. Conversely, its treatment erode health drive process, has dramatically been documented for survivors diagnosed during childhood, adolescence, young adulthood. conclude connected superior including endogenous lifestyle factors, well bidirectional crosstalk, together render not only risk factor an important parameter must considered therapeutic decisions.
Language: Английский
Citations
47
Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)
Published: May 1, 2024
Copper plays vital roles in numerous cellular processes and its imbalance can lead to oxidative stress dysfunction. Recent research has unveiled a unique form of copper-induced cell death, termed cuproptosis, which differs from known death mechanisms. This process involves the interaction copper with lipoylated tricarboxylic acid cycle enzymes, causing protein aggregation death. Recently, growing number studies have explored link between cuproptosis cancer development. review comprehensively examines systemic metabolism copper, including tumor-related signaling pathways influenced by copper. It delves into discovery mechanisms connection various cancers. Additionally, suggests potential treatments using ionophores that induce combination small molecule drugs, for precision therapy specific types.
Language: Английский
Citations
19
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: Aug. 16, 2024
Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and loss iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress triggering death. Recently, has garnered significant interest tumor research due to its potential as crucial therapeutic strategy against cancer. In this review, we summarized cellular molecular mechanisms relationship other types Additionally, reviewed current drugs or strategies available induce cells, including Cu ionophores, small compounds, nanomedicine. Furthermore, targeted metabolism specific regulatory genes cancer therapy enhance sensitivity cuproptosis. Finally, discussed feasibility targeting overcome chemotherapy immunotherapy resistance suggested future directions. This study that could open new avenues for developing therapy.
Language: Английский
Citations
18
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: Feb. 18, 2025
Abstract Breast cancer, characterized by unique epidemiological patterns and significant heterogeneity, remains one of the leading causes malignancy-related deaths in women. The increasingly nuanced molecular subtypes breast cancer have enhanced comprehension precision treatment this disease. mechanisms tumorigenesis progression been central to scientific research, with investigations spanning various perspectives such as tumor stemness, intra-tumoral microbiota, circadian rhythms. Technological advancements, particularly those integrated artificial intelligence, significantly improved accuracy detection diagnosis. emergence novel therapeutic concepts drugs represents a paradigm shift towards personalized medicine. Evidence suggests that optimal diagnosis models tailored individual patient risk expected are crucial, supporting era oncology for cancer. Despite rapid advancements increasing emphasis on clinical comprehensive update summary panoramic knowledge related disease needed. In review, we provide thorough overview global status including its epidemiology, factors, pathophysiology, subtyping. Additionally, elaborate latest research into contributing progression, emerging strategies, long-term management. This review offers valuable insights Cancer Research, thereby facilitating future progress both basic application.
Language: Английский
Citations
14
Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: Jan. 22, 2025
Cuproptosis differs from other forms of cell death, such as apoptosis, necroptosis, and ferroptosis, in its unique molecular mechanisms signaling pathways. In this review, we delve into the cellular metabolic pathways copper, highlighting role copper biomolecule synthesis, mitochondrial respiration, antioxidant defense. Furthermore, elucidate relationship between cuproptosis-related genes (CRGs) cancer prognosis, analyzing their expression patterns across various tumor types impact on patient outcomes. Our review also uncovers potential therapeutic applications chelators, ionophores, copper-based nanomaterials oncology. addition, discuss emerging cuproptosis remodeling microenvironment, enhancing immune infiltration, converting "cold tumors" "hot that respond better to immunotherapy. short, underscores pivotal importance biology highlights translational a novel target.
Language: Английский
Citations
6
Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(783)
Published: Jan. 29, 2025
Pancreatic ductal adenocarcinoma (PDAC) driven by the KRAS-G12D mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is highly selective and first-in-class inhibitor under clinical development. Here, we report that advanced glycosylation end product-specific receptor (AGER) plays key role in mediating resistance PDAC cells. The up-regulation AGER within cancer cells instigates macropinocytosis, facilitating internalization serum albumin subsequent amino acid generation. These acids are then used to synthesize antioxidant glutathione, leading due inhibition apoptosis. underlying molecular mechanism involves AGER's interaction with diaphanous-related formin 1 (DIAPH1), protein responsible for driving Rac family small GTPase (RAC1)-dependent macropinosome formation. effectiveness safety combining pharmacological inhibitors AGER-DIAPH1 complex (using RAGE299) or macropinocytosis EIPA) were confirmed patient-derived xenografts, orthotopic models, genetically engineered mouse models. This combination therapy also induces high-mobility group box (HMGB1) release, resulting antitumor CD8+ T cell response immunocompetent mice. Collectively, study findings underscore potential enhance efficacy blockade targeting AGER-dependent macropinocytosis.
Language: Английский
Citations
3
Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 2, 2025
Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species defined by their genomes, and differences between individuals within a given species directly result from variations in genetic codes. While alterations give rise to disease-causing acquisitions cell identities, it is now well-established biochemical imbalances also lead cellular dysfunction diseases. Specifically, nongenetic chemical events orchestrate metabolism transcriptional programs govern functional identity. Thus, signaling, which broadly defines the conversion extracellular signals into intracellular changes, contribute acquisition diseased states. Metal ions exhibit unique properties be exploited cell. For instance, metal maintain ionic balance cell, coordinate amino acid residues or nucleobases altering folding function biomolecules, catalyze reactions. metals essential signaling effectors normal physiology disease. Deciphering ion challenging endeavor illuminate pathways targeted for therapeutic intervention. Here, we review key processes where play roles describe how targeting has been instrumental dissecting biochemistry this led development effective strategies.
Language: Английский
Citations
2
Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117814 - 117814
Published: Jan. 13, 2025
Language: Английский
Citations
2