Recent Progress in Ferroptosis Inducers for Cancer Therapy

Advanced Materials, Journal Year: 2019, Volume and Issue: 31(51)

Published: Oct. 8, 2019

Abstract Ferroptosis is a newly discovered form of regulated cell death that the nexus between metabolism, redox biology, and human health. Emerging evidence shows potential triggering ferroptosis for cancer therapy, particularly eradicating aggressive malignancies are resistant to traditional therapies. Recently, there has been great deal effort design develop anticancer drugs based on induction. Recent advances ferroptosis‐inducing agents at intersection chemistry, materials science, biology presented. The basis summarized first highlight feasibility characteristics therapy. A literature review inducers (including small molecules nanomaterials) then presented delineate their design, action mechanisms, applications. Finally, some considerations research spotlighted, followed by discussion challenges future development directions this burgeoning field.

Language: Английский

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Lipid peroxidation and ferroptosis: The role of GSH and GPx4

Free Radical Biology and Medicine, Journal Year: 2020, Volume and Issue: 152, P. 175 - 185

Published: March 9, 2020

Language: Английский

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Cell cycle control in cancer

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 74 - 88

Published: Sept. 10, 2021

Language: Английский

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Dual proteome-scale networks reveal cell-specific remodeling of the human interactome

Cell, Journal Year: 2021, Volume and Issue: 184(11), P. 3022 - 3040.e28

Published: May 1, 2021

Language: Английский

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Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 20, 2022

Abstract In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not ICIs, partly caused absence of tumor-infiltrating lymphocytes (TILs), significantly limits application ICIs. Converting these “cold” into “hot” may ICIs is an unsolved question immunotherapy. Since it a general characteristic cancers resist apoptosis, induction non-apoptotic regulated cell death (RCD) emerging as new treatment strategy. Recently, several studies have revealed interaction between RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, necroptosis exhibit synergistic responses while possibly exerting inhibitory effects on responses. Thus, targeted therapies (inducers inhibitors) against combination with exert potent activity, resistant This review summarizes multilevel relationship immunity RCD, including necroptosis, potential targeting improve efficacy malignancy.

Language: Английский

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The role of ubiquitination in tumorigenesis and targeted drug discovery

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Feb. 29, 2020

Ubiquitination, an important type of protein posttranslational modification (PTM), plays a crucial role in controlling substrate degradation and subsequently mediates the "quantity" "quality" various proteins, serving to ensure cell homeostasis guarantee life activities. The regulation ubiquitination is multifaceted works not only at transcriptional levels (phosphorylation, acetylation, methylation, etc.) but also level (activators or repressors). When regulatory mechanisms are aberrant, altered biological processes may induce serious human diseases, especially types cancer. In tumorigenesis, involve tumor metabolism, immunological microenvironment (TME), cancer stem (CSC) stemness so on. With regard some key proteins such as RagA, mTOR, PTEN, AKT, c-Myc P53 significantly regulates activity mTORC1, AMPK PTEN-AKT signaling pathways. addition, TLR, RLR STING-dependent pathways modulates TME. Moreover, core regulator triplets (Nanog, Oct4 Sox2) members Wnt Hippo-YAP participates maintenance CSC stemness. Based on components, including proteasome, E3 ligases, E1, E2 deubiquitinases (DUBs), many molecular targeted drugs have been developed combat Among them, small molecule inhibitors targeting bortezomib, carfilzomib, oprozomib ixazomib, achieved tangible success. MLN7243 MLN4924 (targeting E1 enzyme), Leucettamol A CC0651 nutlin MI-219 compounds G5 F6 DUB activity) shown potential preclinical treatment. this review, we summarize latest progress understanding substrates for their special functions metabolism regulation, TME modulation maintenance. therapeutic targets reviewed, effects drugs.

Language: Английский

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PARP and PARG inhibitors in cancer treatment

Genes & Development, Journal Year: 2020, Volume and Issue: 34(5-6), P. 360 - 394

Published: Feb. 6, 2020

Oxidative and replication stress underlie genomic instability of cancer cells. Amplifying through radiotherapy chemotherapy has been a powerful but nonselective means killing Precision medicine revolutionized therapy by putting forth the concept selective targeting Poly(ADP-ribose) polymerase (PARP) inhibitors represent successful example precision as first drugs DNA damage response to have entered clinic. PARP act synthetic lethality with mutations in repair genes were approved for treatment BRCA mutated ovarian breast cancer. destabilize forks entrapment induce cell death stress-induced mitotic catastrophe. Inhibitors poly(ADP-ribose) glycohydrolase (PARG) exploit exacerbate deficiencies cells may complement broad range types different sources instability. Here I provide an overview molecular mechanisms cellular consequences PARG inhibition. highlight clinical performance four used (olaparib, rucaparib, niraparib, talazoparib) discuss predictive biomarkers inhibitor sensitivity, resistance well overcoming them combination therapy.

Language: Английский

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Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action

International Journal of Environmental Research and Public Health, Journal Year: 2020, Volume and Issue: 17(2), P. 423 - 423

Published: Jan. 8, 2020

There are presently more than 18 known aflatoxins most of which have been insufficiently studied for their incidence, health-risk, and mechanisms toxicity to allow effective intervention control means that would significantly sustainably reduce incidence adverse effects on health economy. Among these, aflatoxin B1 (AFB1) has by far the studied; yet, many aspects range diseases it causes remain be elucidated. Its mutagenicity, tumorigenicity, carcinogenicity—which best known—still suffer from limitations regarding relative contribution oxidative stress reactive epoxide derivative (Aflatoxin-exo 8,9-epoxide) in induction diseases, as well its metabolic synthesis pathways. Additionally, despite well-established additive carcinogenicity between AFB1 other risk factors, e.g., hepatitis viruses B C, hepatotoxic algal microcystins, this synergy unclear. This study reviews recent advances field they cause humans animals.

Language: Английский

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Targeting p53 pathways: mechanisms, structures and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 1, 2023

The TP53 tumor suppressor is the most frequently altered gene in human cancers, and has been a major focus of oncology research. p53 protein transcription factor that can activate expression multiple target genes plays critical roles regulating cell cycle, apoptosis, genomic stability, widely regarded as "guardian genome". Accumulating evidence shown also regulates metabolism, ferroptosis, microenvironment, autophagy so on, all which contribute to suppression. Mutations not only impair its function, but confer oncogenic properties mutants. Since mutated inactivated malignant tumors, it very attractive for developing new anti-cancer drugs. However, until recently, was considered an "undruggable" little progress made with p53-targeted therapies. Here, we provide systematic review diverse molecular mechanisms signaling pathway how mutations impact progression. We discuss key structural features inactivation by mutations. In addition, efforts have therapies, challenges encountered clinical development.

Language: Английский

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p53 signaling in cancer progression and therapy

Cancer Cell International, Journal Year: 2021, Volume and Issue: 21(1)

Published: Dec. 1, 2021

Abstract The p53 protein is a transcription factor known as the "guardian of genome" because its critical function in preserving genomic integrity. TP53 gene mutated approximately half all human malignancies, including those breast, colon, lung, liver, prostate, bladder, and skin. When DNA damage occurs, on chromosome 17 stops cell cycle. If mutated, cycle unrestricted damaged replicated, resulting uncontrolled proliferation cancer tumours. Tumor-associated mutations are usually associated with phenotypes distinct from caused by loss tumor-suppressing exerted wild-type p53protein. Many these mutant proteins have oncogenic characteristics, therefore modulate ability cells to proliferate, escape apoptosis, invade metastasize. Because deficiency so common cancer, this an excellent option for treatment. In review, we will discuss some molecular pathways which might perform their activities, well prospective treatment methods based restoring tumor suppressive functions.

Language: Английский

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