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Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-Translational Modifications and Protein-Protein Interactions.

Histone deacetylase 6 (HDAC6) is a large multidomain protein that deacetylates lysine residues on cytoplasmic proteins, influencing numerous cellular processes. Both the catalytic and noncatalytic functions of HDAC6 have been implicated in cancer development and progression. Over a decade of research on catalytic domain inhibitors has shown that these drugs are well tolerated, exhibit anticancer activity, and can alleviate chemotherapy-induced peripheral neuropathies. However, their effectiveness in treating solid tumours remains uncertain. HDAC6 activity is regulated by protein-protein intera

FASTINA - protocol for a randomised feasibility trial of time-restricted eating to improve response to multiple myeloma therapy.

Multiple myeloma (MM) is an incurable plasma cell malignancy with relapses and diminishing response durations. Preclinical studies suggest that time-restricted eating (TRE)-related metabolic changes may enhance chemosensitivity by exploiting cancer cell vulnerabilities to nutrient deprivation. Clinical data in solid tumours remain limited and heterogeneous, mainly supporting feasibility and possible toxicity reduction rather than definitive efficacy. While efficacy has been explored in breast cancer patients, there is a lack of data for haematological patients, including MM. FASTINA (Fasting i

Targeting Reactive Oxygen Species Capacity of Tumor Cells with Repurposed Drug as an Anticancer Therapy.

Accumulating evidence shows that elevated levels of reactive oxygen species (ROS) are associated with cancer initiation, growth, and response to therapies. As concentrations increase, ROS influence cancer development in a paradoxical way, either triggering tumorigenesis and supporting the proliferation of cancer cells at moderate levels of ROS or causing cancer cell death at high levels of ROS. Thus, ROS can be considered an attractive target for therapy of cancer and two apparently contradictory but virtually complementary therapeutic strategies for the regulation of ROS to treat cancer. Desp

XRK3F2 Inhibition of p62-ZZ Domain Signaling Rescues Myeloma-Induced GFI1-Driven Epigenetic Repression of the Runx2 Gene in Pre-osteoblasts to Overcome Differentiation Suppression.

Multiple myeloma bone disease (MMBD) is characterized by non-healing lytic bone lesions that persist even after a patient has achieved a hematologic remission. We previously reported that p62 (sequestosome-1) in bone marrow stromal cells (BMSC) is critical for the formation of MM-induced signaling complexes that mediate OB suppression. Importantly, XRK3F2, an inhibitor of the p62-ZZ domain, blunted MM-induced Runx2 suppression in vitro, and induced new bone formation and remodeling in the presence of tumor in vivo. Additionally, we reported that MM cells induce the formation of repressive chro

The annual conference of National Cancer Institute - Cairo University "Bridging Gaps in Oncology" : InterContinental Citystars Cairo hotel. 3 - 5 November, 2021.

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Mitophagy related gene signature for prognosis and therapeutic evaluation in KIRC.

This study conducted a comprehensive investigation of the prognostic significance and immunological features associated with mitophagy-related gene signatures in clear cell renal cell carcinoma (KIRC). Our primary aim was to establish an optimized predictive model for precise prognosis stratification and treatment response prediction in KIRC patients. Through LASSO Cox regression analysis, we systematically identified mitophagy-related genes (MRGs) and implemented them to develop a prognostic risk stratification model. The model's reliability was rigorously validated using both internal cohort

USP33 Promotes Lung Adenocarcinoma Brain Metastasis by Inhibiting the K48-Linked Ubiquitination and Degradation of S100A9 and Facilitating Vimentin Secretion.

Brain metastasis has a deterministic influence on the evolutionary trajectory of lung adenocarcinoma (LUAD). Given the profound clinical importance of LUAD brain metastases and the formidable obstacles that hinder their precise prediction, novel therapeutic targets are urgently needed. Notably, a substantial fraction of lung carcinoma cells in brain metastatic foci demonstrates marked S100A9 overexpression. However, whether these cells represent the primary drivers of brain metastasis requires further elucidation. Coculture of S100A9-overexpressing LUAD cells with human brain microvascular end

Позвоните посредникам в Множественной миеломе: увязка ожирения с болезнями костей с помощью воспаленных путей.

У пациентов, у которых диагностирован множественный миелома (ММ), основные жалобы на момент диагностики часто связаны с костями, что существенно влияет на качество жизни и повышает заболеваемость и смертность. Ожирение ассоциируется с хроническим воспалительным состоянием, которое приводит к производству различных цитокинов и адипокинов, что может способствовать разрушению костей. Адипониктин, адипокин, в основном скрытый адипоцитами, значительно сокращается в обращении среди лиц с ожирением, что также наблюдается в MM. Это сокращение может привести к нарушению и без того скомпрометированной а

Renaissance of Traditional Mineral Drugs in Cancer: Advanced Delivery Strategies and Bioengineering Approaches.

Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomod

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… Polyphenols by Inducing Autophagic Cell Death and Apoptosis in Oxalplatin-Resistant HCT116 Colorectal Cancer Cells. Int. J. Mol. Sci. 2025;26:7661. doi: 10.3390/ijms26167661. 74. Catanzaro E., Feron O., Skirtach A.G., Krysko D.V. …

Is Curcumin the Answer to Future Chemotherapy Cocktail?

The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure. The continuous use of conventional cancer therapies leads to chemoresistance, and a higher dose of treatment results in even greater toxicities among cancer patients. Therefore, the search for an alternative treatment modality is crucial to break this viscous cycle. This paper explores the su

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… Induction of autophagic cell death via the upregulation of JNK signalling. | | [ 76 ] Colorectal cancer/colon cancer | 5-FU | Inhibition of cell proliferation via the suppression of Wnt signalling. …

Targeting BTK in B Cell Malignancies: From Mode of Action to Resistance Mechanisms.

The B cell receptor (BCR) signaling pathway plays a crucial role in B cell development and contributes to the pathogenesis of B cell neoplasms. In B cell malignancies, the BCR is constitutively active through both ligand-dependent and ligand-independent mechanisms, resulting in continuous Bruton tyrosine kinase (BTK) signaling activation, which provides a survival and proliferation advantage to the neoplastic clone. Among B cell malignancies, those in which the most significant results were obtained by treatment with BTK inhibitors (BTKi) include chronic lymphocytic leukemia, mantle cell lymph

Mechanism and therapeutic potential of traditional Chinese medicine extracts in sepsis.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Tra

Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.

Temozolomide (TMZ) remains the cornerstone chemotherapy for glioma, yet intrinsic and acquired resistance mechanisms significantly limit its clinical effectiveness. This review summarizes the multifaceted molecular pathways contributing to TMZ resistance, including enhanced DNA repair mechanisms such as O6-methylguanine-DNA methyltransferase (MGMT), mismatch repair (MMR), and base excision repair (BER). Additional resistance factors include genetic mutations that affect the drug response, dysregulated non-coding RNAs (miRNAs, lncRNAs, and circRNAs), glioma stem cells (GSCs), cytoprotective aut

Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis and local recurrence. The tumor immune microenvironment (TME) consists of immune cells, cytokines and immunomodulators, and collectively they influence the response to treatment. Epigenetic changes including DNA methylation and histone modification, as well as increased drug exportation have been reported to contribute to the development of drug resistance in cancers. In the past few years, the majority of studies on tum

Biomolecular condensates as dynamic regulators of musculoskeletal homeostasis, disease, and therapeutic challenges.

Biomolecular condensates are membraneless assemblies that concentrate proteins, nucleic acids, and other biomolecules into dynamic cellular compartments. Liquid-liquid phase separation (LLPS) is one important route by which such condensates form, particularly when multivalent interactions generate liquid-like, reversible assemblies. However, not every condensate or disease-associated assembly should be explained solely by LLPS. In the musculoskeletal system, condensates have been linked to transcription, signal transduction, RNA metabolism, stress responses, tissue development, homeostasis, an

Prospects for repurposing CNS drugs for cancer treatment.

Drug repurposing is the idea of using an already approved drug for another disease or disorder away from its initial use. This new approach ensures the reduction in high cost required for developing a new drug in addition to the time consumed, especially in the tumor disorders that show an unceasing rising rate with an unmet success rate of new anticancer drugs. In our review, we will review the anti-cancer effect of some CNS drugs, including both therapeutic and preventive, by searching the literature for preclinical or clinical evidence for anticancer potential of central nervous system drug

Cancer Chemoprevention: A Strategic Approach Using Phytochemicals.

Cancer chemoprevention approaches are aimed at preventing, delaying, or suppressing tumor incidence using synthetic or natural bioactive agents. Mechanistically, chemopreventive agents also aid in mitigating cancer development, either by impeding DNA damage or by blocking the division of premalignant cells with DNA damage. Several pre-clinical studies have substantiated the benefits of using various dietary components as chemopreventives in cancer therapy. The incessant rise in the number of cancer cases globally is an issue of major concern. The excessive toxicity and chemoresistance associat

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… Kaempferol activates the IRE1-JNK-CHOP signaling from cytosol to nucleus, and G9a inhibition, which activates autophagic cell death in gastric cancer cells ( Kim et al., 2018 ). …

A review on the current literature regarding the value of exosome miRNAs in various diseases.

Exosome microRNAs (miRNAs) have great research outlook in clinical therapy and biomarkers, they have been found to have a close to multiple diseases. A growing number of studies have attempted to alleviate or treat diseases through exosomes. It indicates that miRNAs in exosomes have great significance in preventing and controlling diseases in clinical research. We summarise these studies below to better understand their implications.We screened and analyzed more than 100 articles from PubMed, Web of Science, and other databases from 1987 to 2022. Data of the clinical trials are collected from

A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health.

Curcumin is the most important active component in turmeric extracts. Curcumin, a natural monomer from plants has received a considerable attention as a dietary supplement, exhibiting evident activity in a wide range of human pathological conditions. In general, curcumin is beneficial to human health, demonstrating pharmacological activities of anti-inflammation and antioxidation, as well as antitumor and immune regulation activities. Curcumin also presents therapeutic potential in neurodegenerative, cardiovascular and cerebrovascular diseases. In this review article, we summarize the advancem

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… Involvement of ROS in Curcumin-induced Autophagic Cell Death Korean J. Physiol. Pharmacol. 2011 15 1 7 10.4196/kjpp.2011.15.1.1 21461234 PMC3062078 39. Chen Q. Men Y. Wang H. Chen R. Han X. Liu J. …

The Cancer Antioxidant Regulation System in Therapeutic Resistance.

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cancer cells adeptly maintain elevated levels of both ROS and antioxidants through a process termed "redox reprogramming". This balance optimizes the proliferative influence of ROS while simultaneously reducing the potential for ROS to cause damage to the cell. In some cases, the adapted antioxidant machinery can hamper the efficacy of treatments for neoplastic diseases, representing a significant facet of the resistance mechanisms ob