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Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resist

Passive Monoclonal and Polyclonal Antibody Therapies

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Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract of Equisetum arvense.

In the present study, we evaluated the potential of the plant E. arvense against the cytotoxic and mutagenic effects induced by cyclophosphamide (chemotherapeutic agent) in the bone marrow cells of mice using the Chromosome assay (CA) and Mitotic index (MI) in vivo as the biomarkers. The study was performed following 3 protocols: pre-treatment, simultaneous treatment and post-treatment with the ethanolic extract of the plant. The results demonstrated that the plant extract was not cytotoxic and mutagenic and has a protective effect against the mutagenicity induced by cyclophosphamide in pre, s

Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.

Epigenetics shapes all aspects of cancer occurrence and progression. Among them, chromatin methylation is a particularly important regulator of oncogenic processes. The dynamic shifts in methylation can influence the development or death of tumor cells. In the therapeutic context, effectively targeting and modulating DNA, RNA, and histone methylation brings promise for the early detection, prognostic assessment, and treatment of cancer. In particular, novel methylation inhibitors or modulators powerfully kill tumor cells or improve existing therapeutic strategies through different signaling pa

Blood Vessels and Peripheral Nerves as Key Players in Cancer Progression and Therapy Resistance.

Cancer cells continuously interact with the tumor microenvironment (TME), a heterogeneous milieu that surrounds the tumor mass and impinges on its phenotype. Among the components of the TME, blood vessels and peripheral nerves have been extensively studied in recent years for their prominent role in tumor development from tumor initiation. Cancer cells were shown to actively promote their own vascularization and innervation through the processes of angiogenesis and axonogenesis. Indeed, sprouting vessels and axons deliver several factors needed by cancer cells to survive and proliferate, inclu

Biopharmaceutical and pharmacokinetic attributes to drive nanoformulations of small molecule tyrosine kinase inhibitors.

Buoyed by the discovery of small-molecule tyrosine kinase inhibitors (smTKIs), significant impact has been made in cancer chemotherapeutics. However, some of these agents still encounter off-target toxicities and suboptimal efficacies due to their inferior biopharmaceutical and/or pharmacokinetic properties. Almost all of these molecules exhibit significant inter- and intra-patient variations in plasma concentration-time profiles. Thus, therapeutic drug monitoring, dose adjustments and precision medicine are being contemplated by clinicians. Complex formulations or nanoformulation-based drug d

Development of CAR T Cell Therapy in Children-A Comprehensive Overview.

CAR T cell therapy has revolutionized immunotherapy in the last decade with the successful establishment of chimeric antigen receptor (CAR)-expressing cellular therapies as an alternative treatment in relapsed and refractory CD19-positive leukemias and lymphomas. There are fundamental reasons why CAR T cell therapy has been approved by the Food and Drug administration and the European Medicines Agency for pediatric and young adult patients first. Commonly, novel therapies are developed for adult patients and then adapted for pediatric use, due to regulatory and commercial reasons. Both strateg

SETD2 and EZH2: Two epigenetic drivers of prostate cancer.

Prostate cancer is a prevalent malignancy among men, characterized by complex mechanisms underlying metastasis and treatment resistance. Epigenetic modifications play a crucial role in regulating prostate cancer progression, particularly involving histone methyltransferases such as SET-domain containing 2 (SETD2) and Enhancer of Zeste homolog 2 (EZH2). SETD2 contributes to chromatin stability by catalyzing the trimethylation of histone H3 lysine 36 (H3K36me3), and its downregulation is strongly correlated with increased invasiveness and epithelial-mesenchymal transition in prostate cancer. Con

The role of LncRNA LBX2-AS1 in cancers: functions, mechanisms and potential clinical utility.

Increasingly advanced biology technique has revealed that long non-coding RNAs (lncRNA) as critical factors that exert significant regulatory effects on biological functions by modulating gene transcription, epigenetic modifications and protein translation. A newly emerging lncRNA, ladybird homeobox 2 (LBX2)-antisense RNA 1 (LBX2-AS1), was found to be highly expressed in various tumors. Moreover, it is functionally linked to the regulation of essential tumor-related biological processes, such as cell proliferation and apoptosis, through interactions with multiple signaling molecules/pathways.

An expanding horizon of complex injectable products: development and regulatory considerations.

There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients' quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as "Safe and Effective" produ

Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials.

Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of

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… Lucialdheydes A and C, ganodermanonol, and ganodermanondiol showed cytotoxic activity in vitro in Lewis lung carcinoma, sarcoma 180, T-47D, and Meth-A tumor cell lines [ 21 ]. … Kumm. were reported by Sarangi et al. [ 33 ] by assaying, in vitro and in vivo, the effect of water-soluble proteoglycan fractions extracted from P . ostreatus , or oyster mushroom, on a sarcoma-180-bearing mouse model. …

Targeting cancer stem cells in drug discovery: Current state and future perspectives.

In recent decades, cancer stem cells (CSCs) have been increasingly identified in many malignancies. CSC-related signaling pathways and their functions provide new strategies for treating cancer. The aberrant activation of related signaling pathways (e.g., Wnt, Notch, and Hedgehog pathways) has been linked to multiple types of malignant tumors, which makes these pathways attractive targets for cancer therapy. CSCs display many characteristic features, such as self-renewal, differentiation, high tumorigenicity, and drug resistance. Therefore, there is an urgent need to develop new therapeutic st

Aging modulation of the immune system and immunotherapy efficacy in cancer.

Immunosenescence is characterized by immune decline and chronic inflammation. With advancing age, the incidence of tumors increases significantly. Understanding how immunosenescence influences the initiation and progression of tumors, as well as its implications for tumor immunotherapy, has become a matter of urgent importance. This review begins with an analysis of the phenotypic changes and underlying mechanisms associated with immune system and immune cell aging, and further explores the interplay between immunosenescence and tumorigenesis. Evidence indicates that cytokines, cell interactio

Harnessing CAR-Extracellular Vesicles for Next-Generation Cancer Immunotherapy.

Cancer immunotherapy has experienced substantial progress in recent years, particularly with the advancement of chimeric antigen receptor (CAR) technology, which enables immune cells to selectively target tumor-associated antigens. CARs, now in their fifth generation, are engineered by combining monoclonal antibody fragments with signaling and co-stimulatory domains and have been successfully applied to T cell, natural killer (NK) cell, and macrophage-based therapies. Notable clinical successes, such as tisagenlecleucel and lisocabtagene maraleucel underscore the therapeutic potential of CAR-T

The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.

Supplements are widely perceived as safe and beneficial; yet in oncology, this assumption is questionable. Clinical trials over the past few decades have often produced disappointing results, raising a critical question: are these agents used correctly, or could they inadvertently cause harm? This review examines supplements frequently used in cancer care-such as oral vitamin C, berberine, N-acetylcysteine, vitamin D, vitamin E, melatonin, polyphenols, alpha-lipoic acid, selenium, and coenzyme Q10-which can act as tumor suppressors or promoters depending on dose, route, and disease stage. We e

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

Radiometals in Imaging and Therapy: Highlighting Two Decades of Research.

The present article highlights the important progress made in the last two decades in the fields of molecular imaging and radionuclide therapy. Advancements in radiometal-based positron emission tomography, single photon emission computerized tomography, and radionuclide therapy are illustrated in terms of their production routes and ease of radiolabeling. Applications in clinical diagnostic and radionuclide therapy are considered, including human studies under clinical trials; their current stages of clinical translations and findings are summarized. Because the metalloid astatine is used for

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.

Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS-RAF-MAPK kinase (MEK)-extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for th

Nanoparticle-based strategy in CAR-T cell immunotherapy: challenges, implications, and perspectives.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable progress in treating hematologic malignancies, yet its broader application faces challenges such as manufacturing complexity, solid tumor microenvironment barriers, and immune toxicity. Nanoparticles (NPs), leveraging their precise delivery, immunomodulation, and multifunctional integration capabilities, offer innovative strategies to optimize CAR-T cell therapy. This review provides a comprehensive elucidation of the fundamental framework of CAR-T cell therapy and the challenges in oncological applications. Subsequently, w

A Clinical Viewpoint on the Use of Targeted Therapy in Advanced Gastric Cancer.

The development of therapies for advanced gastric cancer (GC) has made significant progress over the past few years. The identification of new molecules and molecular targets is expanding our understanding of the disease's intricate nature. The end of the classical oncology era, which relied on well-studied chemotherapeutic agents, is giving rise to novel and unexplored challenges, which will cause a significant transformation of the current oncological knowledge in the next few years. The integration of established clinically effective regimens in additional studies will be crucial in managin