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Targeting Protein Degradation Pathways in Tumors: Focusing on their Role in Hematological Malignancies.

Cells must maintain their proteome homeostasis by balancing protein synthesis and degradation. This is facilitated by evolutionarily-conserved processes, including the unfolded protein response and the proteasome-based system of protein clearance, autophagy, and chaperone-mediated autophagy. In some hematological malignancies, including acute myeloid leukemia, misfolding or aggregation of the wild-type p53 tumor-suppressor renders cells unable to undergo apoptosis, even with an intact p53 DNA sequence. Moreover, blocking the proteasome pathway triggers lymphoma cell apoptosis. Extensive studie

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… During normal hematopoiesis, and in malignancies, the UPS plays a crucial role in the regulation of e.g., c-kit, cyclin D, Bcl-2, and others [ 42 ]. Moreover, cell signaling might be modified by proteasomal degradation of key cytokine receptors after their activation. …

Current concepts of the crosstalk between lncRNA and E2F1: shedding light on the cancer therapy.

Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context of cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These lncRNAs serve as competitive endogenous RNAs (ceRNAs) through sponging microRNAs and regulating the expression of targeted genes. Moreover, they also directly bind to RNA-binding proteins, which can be integrated into a complex mechanistic network. E2F1, an extensively studied

Sexual dimorphism in cancer: molecular mechanisms and precision oncology perspectives.

Sex differences play a crucial role in determining tumor incidence, treatment sensitivity, and prognosis among men and women. However, current clinical cancer treatment strategies fail to account for these differences. Furthermore, the underlying mechanisms of tumor disparities between sexes remain elusive. Sex differences in sex chromosomes, hormone levels, metabolism, and immunity synergistically contribute to tumor-related disparities. As the demand for precision medicine escalates, there is an urgent need to conduct further exploration and research to address the tumor differences between

Targeting Autophagy Using Long Non-Coding RNAs (LncRNAs): New Landscapes in the Arena of Cancer Therapeutics.

Cancer has become a global health hazard accounting for 10 million deaths in the year 2020. Although different treatment approaches have increased patient overall survival, treatment for advanced stages still suffers from poor clinical outcomes. The ever-increasing prevalence of cancer has led to a reanalysis of cellular and molecular events in the hope to identify and develop a cure for this multigenic disease. Autophagy, an evolutionary conserved catabolic process, eliminates protein aggregates and damaged organelles to maintain cellular homeostasis. Accumulating evidence has implicated the

Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.

Zinc metabolism at the cellular level is critical for many biological processes in the body. A key observation is the disruption of cellular homeostasis, often coinciding with disease progression. As an essential factor in maintaining cellular equilibrium, cellular zinc has been increasingly spotlighted in the context of disease development. Extensive research suggests zinc's involvement in promoting malignancy and invasion in cancer cells, despite its low tissue concentration. This has led to a growing body of literature investigating zinc's cellular metabolism, particularly the functions of

Многоцелевые лекарственные препараты: новые 2025 и послерыночного контроля за безопасностью наркотиков, 2022-2024.

Полифармакология предназначена для развития соединений, действующих по крайней мере на two целевые показатели (многоцелевые лиганды, МТДЛ). В 2025, Европейское агентство по медицине (ЕМА), 38 наркотиков, и 11 из них были MTDL. Большинство из них - антитела-наркотики, биконкретные антитела или ингибиторы киназы, все из которых указаны для лечения опухолей, включая датопотамаб дерукстекан (гормон-позитивный рецептор, HER2-negative Рак молочной железы), тизотумаб ведотин (сокращенная шейная карцинома), линвосельтамб (четвёртая линия лечения множественной миеломы) и эрдафитиниб (сокращенная уротел

The 'speck'-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis.

The NLRP3 inflammasome is an intracellular sensor and an essential component of the innate immune system involved in danger recognition. An important hallmark of inflammasome activation is the formation of a single supramolecular punctum, known as a speck, per cell, which is the site where the pro-inflammatory cytokines IL-1β and IL-18 are converted into their bioactive form. Speck also provides the platform for gasdermin D protein activation, whose N-terminus domain perforates the plasma membrane, allowing the release of mature cytokines alongside with a highly inflammatory form of cell death

Bradyarrhythmias Associated with Oncologic Treatment-An Updated Review.

Background/Objectives: Bradyarrhythmias are an under-recognized component of cancer therapy-related cardiovascular toxicity. As survivorship improves and exposure to targeted and immune therapies increases, clinicians increasingly face clinically relevant sinus node dysfunction and atrioventricular (AV) conduction disease that may interrupt otherwise effective oncologic treatment. We aimed to synthesize evidence on the incidence, phenotype, mechanisms, and management of bradyarrhythmias across major anticancer drug classes. Methods: We performed a narrative review of PubMed and major clinical

Marine Natural Products as Potent Anticancer Agents (2020-2024): Structural Diversity, SARs and Target Prediction.

In recent years, Marine Natural Products (MNPs) have emerged as a significant source for anticancer drug discovery, as many natural products can offer structural diversity, unique mechanisms of action, and relatively low toxicity. This article provides a systematic review of MNPs with reported anticancer activities from 2020 to 2024. These compounds are classified into seven major categories: terpenoids, alkaloids, sterols, polyketides, peptides and proteins, polysaccharides, and macrolides. For each category, we elaborate on the marine sources, structural identification, in vitro anticancer a

Investigation of the cytotoxicity induced by cannabinoids on human ovarian carcinoma cells.

Cannabinoids have been shown to induce anti-tumor activity in a variety of carcinoma cells such as breast, prostate, and brain. The aim of the present study is to investigate the anti-tumor activity of cannabinoids, CBD (cannbidiol), and CBG (cannabigerol) in ovarian carcinoma cells sensitive and resistant to chemotherapeutic drugs. Sensitive A2780 cells and resistant A2780/CP70 carcinoma cells and non-carcinoma cells were exposed to varying concentrations of CBD, CBG, carboplatin or CB1 and CB2 receptor antagonists, AM251 and AM630, respectively, alone or in combination, at different exposure

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… In addition, during the cell cycle, the cyclin‐dependent kinase inhibitor, p27 is activated and then binds to cyclin D, which subsequently inhibits the catalytic activity of Cdk4. …

Остеопонтин по хроническим воспламенительным болезням: механизмы, биомаркеры и терапевтические стратегии.

Хронические подстрекательские заболевания, такие, как ревматуидный артрит (RA), системный волчан Эрематосус (SLE), множественный склероз (MS), атеросклероз и воспалительный кишечник (IBD), вызывают серьезную озабоченность во всем мире. Эти расстройства характеризуются стойким воспалением, дисфункцией иммунной системы, повреждением тканей и фиброзом, что в конечном счете приводит к серьезной дисфункции органов и снижению качества жизни. Остеопонтин (OPS), многофункциональный внеклеточный белок, играет решающую роль в иммунном регулировании, воспалении и реконструкции тканей. Она поощряет набор

TLN1: an oncogene associated with tumorigenesis and progression.

Talin-1 (TLN1), encoded by the TLN1 gene, is a focal adhesion-related protein capable of binding various proteins in the cytoskeleton. It is also expressed at high levels in many cancers wherein it influences cellular adhesion and the activation of integrins. TLN1 is also capable of promoting tumor cell invasivity, proliferation, and metastatic progression, in addition to being a relevant biomarker and therapeutic target in certain cancers. The present review offers a comprehensive overview of current knowledge regarding TLN1 with respect to its structural properties, functions, and role in tu

Анализ Four Пациенты отключают Idecabtagen Vicleucel после Leukapheres из-за Multieloma Progression.

В настоящем докладе four - пациенты, которые не смогли получить idecabtagen vicleucel (ide-cel) из-за развития болезни, несмотря на то, что они проходили лейкаферез в соответствии с техническими требованиями. Средний возраст пациентов составлял 70 (дальность, 68-77) лет. Two у пациентов были не секретарские подтипы на диагнозе. Среднее число предыдущих терапевтических линий составило 4.5 (дальность, 4-6) и 3 Пациенты были пента-реакторами. Все пациенты отказались от последнего лечения. Среднее время от аферы до отмены ide-cel 44.5 (ассортимент: 24-71) дней. Наши выводы свидетельствуют о том, ч

A Review of The Synergistic Effects of Curcumin with Proteasome Inhibitors in Multiple Myeloma Preclinical Models.

Proteasome inhibitors are the cornerstone of multiple myeloma treatment, but challenges still remain despite the increased survival rates. We conducted a review on the role of curcumin, a natural product, as an adjunct to bortezomib and carfilzomib in preclinical multiple myeloma models. Four studies reviewed showed enhanced anticancer effects when curcumin was combined with bortezomib compared to either treatment alone. Two additional studies showed similar results with carfilzomib. Synergistic mechanisms include inhibition of NF-kB, IL-6-induced signaling pathways, JNK pathway modulation, an

Proteasome Inhibitors for the Treatment of Multiple Myeloma.

Use of proteasome inhibitors (PIs) has been the therapeutic backbone of myeloma treatment over the past decade. Many PIs are being developed and evaluated in the preclinical and clinical setting. The first-in-class PI, bortezomib, was approved by the US food and drug administration in 2003. Carfilzomib is a next-generation PI, which selectively and irreversibly inhibits proteasome enzymatic activities in a dose-dependent manner. Ixazomib was the first oral PI to be developed and has a robust efficacy and favorable safety profile in patients with multiple myeloma. These PIs, together with other

MICAL1 promotes the proliferation in acute myeloid leukemia and is associated with clinical prognosis and immune infiltration.

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has a poor prognosis and a high rate of relapse. Dysregulated metabolism plays an important role in AML progression. This study aimed to conduct a comprehensive analysis of MRGs using TCGA and GEO datasets and further explore the potential function of critical MRGs in AML progression. In this study, we identified 17 survival-related differentially expressed MRGs in AML using TCGA and GEO datasets. The 150 AML samples were divided into three molecular subtypes using 17 MRGs, and we found that three molecular

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… Deng et al. showed that in breast cancer, MICAL1 was overexpressed, and its effect on proliferation was seen through the maintenance of cyclin D expression via ROS-sensitive PI3K/Akt/ERK signaling [ 48 ]. … Deng W Wang Y Zhao S Zhang Y Chen Y Zhao X Liu L Sun S Zhang L Ye B MICAL1 facilitates breast cancer cell proliferation via ROS-sensitive ERK/cyclin D pathway J Cell Mol Med 2018 22 6 3108 3118 10.1111/jcmm.13588 29524295 PMC5980113 …

Novel Non-Immunologic Agents for Relapsed and Refractory Multiple Myeloma: A Review Article.

Novel treatments are needed to address the lack of options for patients with relapsed or refractory multiple myeloma. Even though immunotherapy-based treatments have revolutionized the field in recent years, offering new opportunities for patients, there is still no curative therapy. Thus, non-immunologic agents, which have proven effective for decades, are still central to the treatment of multiple myeloma, especially for advanced disease. Building on their efficacy in myeloma, the development of proteasome inhibitors and immunomodulatory drugs has been pursued, and has led to the emergence o

The evolving role and utility of off-label drug use in multiple myeloma.

The treatment landscape for multiple myeloma (MM) has dramatically changed over the last three decades, moving from no US Food and Drug Administration approvals and two active drug classes to over 19 drug approvals and at least eight different active classes. The advances seen in MM therapy have relied on both a structured approach to obtaining new labels and cautious off-label drug use. Although there are country and regional differences in drug approval processes, many of the basic principles behind off-label drug use in MM can be summarized into four main categories: 1) use of a therapy pri

Mapping oncogenic protein interactions for precision medicine.

Normal protein-protein interactions (normPPIs) occur with high fidelity to regulate almost every physiological process. In cancer, this highly organised and precisely regulated network is disrupted, hijacked or reprogrammed resulting in oncogenic protein-protein interactions (oncoPPIs). OncoPPIs, which can result from genomic alterations, are a hallmark of many types of cancers. Recent technological advances in the field of mass spectrometry (MS)-based interactomics, structural biology and drug discovery have prompted scientists to identify and characterise oncoPPIs. Disruption of oncoPPI inte

Exploring the Potential of MicroRNA Let-7c as a Therapeutic for Prostate Cancer.

Prostate cancer (PCa) is one of the leading causes of mortality worldwide and often presents with aberrant microRNA (miRNA) expression. Identifying and understanding the unique expression profiles could aid in the detection and treatment of this disease. This review aims to identify miRNAs as potential therapeutic targets for PCa. Three bio-informatic searches were conducted to identify miRNAs that are reportedly implicated in the pathogenesis of PCa. Only hsa-Lethal-7 (let-7c), recognized for its role in PCa pathogenesis, was common to all three databases. Three further database searches were