Microfluidic fabrication of lipid nanoparticles for co-delivery of siRNA and hydroxychloroquine: An engineered theranostic platform for enhanced breast cancer treatment

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160172 - 160172

Published: Feb. 1, 2025

Language: Английский

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In silico modeling of targeted protein degradation

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117432 - 117432

Published: Feb. 20, 2025

Language: Английский

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Computational approaches to aid PROTAC drug discovery

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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A CDK4-selective inhibitor puts the brakes on cancer cells

Cancer Cell, Journal Year: 2025, Volume and Issue: 43(3), P. 335 - 337

Published: March 1, 2025

Language: Английский

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Identification of E3 Ubiquitin Ligase Substrates Using Biotin Ligase-Based Proximity Labeling Approaches

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 854 - 854

Published: April 2, 2025

Ubiquitylation is a post-translational modification originally identified as the first step in protein degradation by ubiquitin–proteasome system. also known to regulate many cellular processes without degrading ubiquitylated proteins. Substrate proteins are specifically recognized and ubiquitin ligases. It necessary identify substrates for each ligase understand physiological pathological roles of ubiquitylation. Recently, promiscuous mutant biotin derived from Escherichia coli, BioID, its variants have been utilized analyze protein–protein interaction. In this review, we summarize current knowledge regarding molecular mechanisms underlying ubiquitylation, BioID-based approaches interactome studies, application BirA identification substrates.

Language: Английский

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Vepdegestrant for the treatment of HR+/HER2– breast cancer

Expert Opinion on Pharmacotherapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

The treatment of advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer has been improved through the development endocrine therapy (ET) targeted agents. However, resistance to ET, particularly caused by ESR1 mutations, not fully addressed. Vepdegestrant is a first-in-class, selective, orally bioavailable PROteolysis TArgeting Chimera (PROTAC) estrogen (ER) degrader. Preclinical studies have suggested promising activity vepdegestrant irrespective genotypes. Phase I II clinical revealed favorable safety profile encouraging efficacy as single agent in combination with other results phase III VERITAC-2 study, comparing fulvestrant, are expected be available 2025, will provide first data on true significance vepdegestrant. Several combinations including + atirimociclib (a cyclin-dependent kinase 4 inhibitor) or planned conducted. these may only transform landscape for HR+/HER2- but pave way PROTAC new class anti-cancer drugs that make previously undruggable targets druggable.

Language: Английский

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From Invaginating Site to Deep Lesion: Spatial Transcriptomics Unravels Ectopic Endometrial Penetration Features in Adenomyosis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Abstract Adenomyosis, characterized by clinical intractability, significantly impacts female fertility and life quality due to the absence of definitive diagnostic markers effective treatment options. The invagination theory is a primary hypothesis for adenomyosis, but underlying molecular mechanisms remain unclear. In this study, spatial transcriptional landscape adenomyosis with an evident structure mapped from endometrial invaginating site ectopic lesions utilizing transcriptomics single‐cell RNA sequencing. addition, authors employ bulk sequencing deconvolution assess significance core ecotypes, use histological techniques target specific cell types, conduct in vitro experiments validation. At site, SFRP5 + epithelial cells promote proliferation angiogenesis through secretion IHH. During invading process, ESR1 smooth muscle (SMCs) facilitate invasion creating migratory tracts via collagen degradation. Within deep lesions, CNN1 stromal fibroblasts induce fibrosis undergoing fibroblast‐to‐myofibroblast transition (FMT) response pathologic profibrogenic signals microenvironment lesions. This work offers in‐depth understanding pathological processes invagination. Furthermore, introduces first web source which expected be valuable resource subsequent research.

Language: Английский

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Molecular Mechanisms and Therapeutic Strategies to Overcome Resistance to Endocrine Therapy and CDK4/6 Inhibitors in Advanced ER+/HER2− Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3438 - 3438

Published: April 7, 2025

Approximately 70-80% of breast cancers are estrogen receptor-positive (ER+), with 65% these cases also being progesterone (ER+PR+). In most ER+ advanced cancer, endocrine therapy (ET) serves as the first-line treatment, utilizing various drugs that inhibit ER signaling. These include tamoxifen, a selective receptor modulator (SERM); fulvestrant, degrader (SERD); and aromatase inhibitors (AIs), which block synthesis. However, intrinsic or acquired hormone resistance eventually develops, leading to disease progression. The combination ET cyclin-dependent kinase 4 6 (CDK4/6is) has been shown significantly increase progression-free survival (PFS) and, in some cases, overall (OS). CDK4/6is works by arresting cell cycle G1 phase, preventing DNA synthesis, enhancing efficacy ET. This review highlights key mechanisms ET, whether used alone biological agents, well emerging therapeutic strategies aimed at overcoming resistance. Addressing remains work progress, near future, better patient selection for different approaches is expected through identification more precise genetic markers. particular, liquid biopsy may provide real-time portrait disease, offering insights into driving cancer

Language: Английский

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Advances in targeting the estrogen receptor in breast cancer

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Targeted protein degradation for cancer therapy

Nature reviews. Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Language: Английский

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