Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy

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

Published: March 24, 2022

Abstract Cancer microenvironment is critical for tumorigenesis and cancer progression. The extracellular matrix (ECM) interacts with tumor stromal cells to promote proliferation, migration, invasion, angiogenesis immune evasion. Both ECM itself stiffening-induced mechanical stimuli may activate cell membrane receptors mechanosensors such as integrin, Piezo1 TRPV4, thereby modulating the malignant phenotype of cells. A better understanding how stiffness regulates progression will contribute development new therapeutics. rapidly expanding evidence in this research area suggests that regulators effectors represent potential therapeutic targets cancer. This review summarizes recent work on regulation cancer, effects progression, immunity drug resistance. We also discuss be druggable intervene Based these advances, future efforts can made develop more effective safe drugs interrupt stiffness-induced oncogenic signaling,

Language: Английский

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E3 ubiquitin ligases: styles, structures and functions

Molecular Biomedicine, Journal Year: 2021, Volume and Issue: 2(1)

Published: July 29, 2021

Abstract E3 ubiquitin ligases are a large family of enzymes that join in three-enzyme ubiquitination cascade together with activating enzyme E1 and conjugating E2. play an essential role catalyzing the process transferring protein to attach lysine site targeted substrates. Importantly, modification is involved almost all life activities eukaryotes. Thus, might be regulating various biological processes cellular responses stress signal associated cancer development. Thanks their multi-functions, can promising target therapy. A deeper understanding regulatory mechanisms tumorigenesis will help find new prognostic markers accelerate growth anticancer therapeutic approaches. In general, we mainly introduce classifications important roles progression functions.

Language: Английский

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E3 ligases and deubiquitinating enzymes regulating the MAPK signaling pathway in cancers

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2022, Volume and Issue: 1877(3), P. 188736 - 188736

Published: May 1, 2022

Language: Английский

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Development of therapeutic antibodies for the treatment of diseases

Molecular Biomedicine, Journal Year: 2022, Volume and Issue: 3(1)

Published: Nov. 22, 2022

Abstract Since the first monoclonal antibody drug, muromonab-CD3, was approved for marketing in 1986, 165 drugs have been or are under regulatory review worldwide. With approval of new treating a wide range diseases, including cancer and autoimmune metabolic disorders, therapeutic drug market has experienced explosive growth. Monoclonal antibodies sought after by many biopharmaceutical companies scientific research institutes due to their high specificity, strong targeting abilities, low toxicity, side effects, development success rate. The related industries markets growing rapidly, one most important areas field biology medicine. In recent years, great progress made key technologies theoretical innovations provided antibodies, antibody–drug conjugates, antibody-conjugated nuclides, bispecific nanobodies, other analogs. Additionally, can be combined with used fields create cross-fields, such as chimeric antigen receptor T cells (CAR-T), CAR-natural killer (CAR-NK), cell therapy. This summarizes latest that worldwide, well clinical on these approaches development, outlines discovery strategies emerged during hybridoma technology, phage display, preparation fully human from transgenic mice, single B-cell artificial intelligence-assisted discovery.

Language: Английский

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Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 260, P. 115772 - 115772

Published: Aug. 28, 2023

Language: Английский

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New-generation advanced PROTACs as potential therapeutic agents in cancer therapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 21, 2024

Abstract Proteolysis-targeting chimeras (PROTACs) technology has garnered significant attention over the last 10 years, representing a burgeoning therapeutic approach with potential to address pathogenic proteins that have historically posed challenges for traditional small-molecule inhibitors. PROTACs exploit endogenous E3 ubiquitin ligases facilitate degradation of interest (POIs) through ubiquitin–proteasome system (UPS) in cyclic catalytic manner. Despite recent endeavors advance utilization clinical settings, majority fail progress beyond preclinical phase drug development. There are multiple factors impeding market entry PROTACs, insufficiently precise favorable POIs standing out as one most formidable obstacles. Recently, there been exploration new-generation advanced including PROTAC prodrugs, biomacromolecule-PROTAC conjugates, and nano-PROTACs, improve vivo efficacy PROTACs. These improved possess capability mitigate undesirable physicochemical characteristics inherent thereby enhancing their targetability reducing off-target side effects. The will mark pivotal turning point realm targeted protein degradation. In this comprehensive review, we meticulously summarized state-of-the-art advancements achieved by these cutting-edge elucidated underlying design principles, deliberated upon prevailing encountered, provided an insightful outlook on future prospects within field.

Language: Английский

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Characteristic roadmap of linker governs the rational design of PROTACs

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(10), P. 4266 - 4295

Published: April 11, 2024

Proteolysis targeting chimera (PROTAC) technology represents a groundbreaking development in drug discovery, leveraging the ubiquitin‒proteasome system to specifically degrade proteins responsible for disease. PROTAC is characterized by its unique heterobifunctional structure, which comprises two functional domains connected linker. The linker plays pivotal role determining PROTAC's biodegradative efficacy. Advanced and rationally designed linkers are under development. Nonetheless, correlation between characteristics efficacy remains under-investigated. Consequently, this study will present multidisciplinary analysis of their impact on efficacy, thereby guiding rational design linkers. We primarily discuss structural types linkers, optimization strategies used design. Furthermore, we how factors like length, group type, flexibility, linkage site affect biodegradation efficiency PROTACs. believe that work contribute towards advancement research area.

Language: Английский

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PROTAC technology: From drug development to probe technology for target deconvolution

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 276, P. 116725 - 116725

Published: July 30, 2024

Language: Английский

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Nano-PROTACs: state of the art and perspectives

Nanoscale, Journal Year: 2024, Volume and Issue: 16(9), P. 4378 - 4391

Published: Jan. 1, 2024

Schematic illustration of the combinational strategy nanotechnology and PROTACs (Nano-PROTACs): typical shortcomings traditional nanotechnology-based strategies for PROTAC drugs optimization.

Language: Английский

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Novel strategies to manage CAR-T cell toxicity

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Language: Английский

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