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Second-Generation Antimitotics in Cancer Clinical Trials.

Mitosis represents a promising target to block cancer cell proliferation. Classical antimitotics, mainly microtubule-targeting agents (MTAs), such as taxanes and vinca alkaloids, are amongst the most successful anticancer drugs. By disrupting microtubules, they activate the spindle assembly checkpoint (SAC), which induces a prolonged delay in mitosis, expected to induce cell death. However, resistance, toxicity, and slippage limit the MTA's effectiveness. With the desire to overcome some of the MTA's limitations, mitotic and SAC components have attracted great interest as promising microtubule

A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy.

The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy. Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies. Human epidermal growth factor receptor, hormone receptors, and angiogenesis factors are among the established therapies in tumor reduction and managing side effects. Novel targeted therapies like KRAS G12C, Claudin-18 isoform 2 (CLDN18.2), Trophoblast cell-surface antigen 2 (TROP2), and epigenetic r

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… Gefitinib arrests the cell cycle at the G1 phase by blocking the mitogen-activated protein kinase pathway (MAPK) and P13K/AKT pathways involved in apoptosis and cell survival. Gefitinib was also reported to be more tolerable and cost-effective as compared to erlotinib. …

Role of Bruton's tyrosine kinase in B cells and malignancies.

Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor a

Killers at the crossroads: The use of innate immune cells in adoptive cellular therapy of cancer.

Adoptive cell therapy (ACT) is an approach to cancer treatment that involves the use of antitumor immune cells to target residual disease in patients after completion of chemo/radiotherapy. ACT has several advantages compared with other approaches in cancer immunotherapy, including the ability to specifically expand effector cells in vitro before selection for adoptive transfer, as well as the opportunity for host manipulation in order to enhance the ability of transferred cells to recognize and kill established tumors. One of the main challenges to the success of ACT in cancer clinical trials

Single-cell sequencing technology to characterize stem T-cell subpopulations in acute T-lymphoblastic leukemia and the role of stem T-cells in the disease process.

BackgroundPrecursor T-cell acute lymphoblastic leukemia (Pre-T ALL) is a malignant neoplastic disease in which T-cells proliferate in the bone marrow. Single-cell sequencing technology could identify characteristic cell types, facilitating the study of the therapeutic mechanisms in Pre-T ALL.MethodsThe single-cell sequencing data (scRNA-seq) of Pre-T ALL were obtained from public databases. Key immune cell subpopulations involved in the progression of Pre-T ALL were identified by clustering and annotating the cellular data using AUCell. Next, pseudo-temporal analysis was performed to identify

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… CDKN2D plays an important role in cell cycle regulation by inhibiting cell-cycle-dependent kinases to regulate cell proliferation to prevent uncontrolled cell division, particularly in the G1 phase [ 45 ]. …

Potential Utility of A Proliferation-Inducing Ligand (APRIL) in Colorectal Cancer.

APRIL (A proliferation-inducing ligand) is a member of the tumor necrosis factor superfamily that is overexpressed in a variety of malignant tumors, including colorectal cancer (CRC). Its key physiological roles include inducing the immunoglobulin switch and ensuring plasmocyte survival. In terms of pathological roles, APRIL antagonism has been identified as a key target in autoimmune diseases and immunoglobulin disorders. As previously demonstrated, several inflammatory processes occur at the site of neoplastic initial stages, and their local symptoms are difficult to detect, particularly in

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… Similar research was conducted in which authors revealed that APRIL depletion utilizing RNA interference in the COLO 205 and SW480 cell lines resulted in growth suppression as well as cell cycle arrest in the G0/G1 phase and apoptosis. …

MicroRNAs and Chinese Medicinal Herbs: New Possibilities in Cancer Therapy.

In recent decades Chinese medicine has been used worldwide as a complementary and alternative medicine to treat cancer. Plenty of studies have shown that microRNAs (miRNAs) play fundamental roles in many pathological processes, including cancer, while the anti-cancer mechanisms of Chinese medicinal herbs targeting miRNAs also have been extensively explored. Our previous studies and those of others on Chinese medicinal herbs and miRNAs in various cancer models have provided a possibility of new cancer therapies, for example, up-regulating the expression of miR-23a may activate the positive regu

The causal relationship between multiple cardiovascular diseases and glioblastoma: A Mendelian randomization study.

Observational studies suggest an association between glioblastoma (GBM) and cardiovascular diseases (CVDs), but a causal relationship remains unestablished. This study aimed to investigate the causal link between multiple CVDs and GBM risk. The inverse variance weighted method indicated that all 18 CVDs had significant causal associations with GBM (P < .05). Genetically predicted CVDs were uniformly associated with a lower risk of GBM (odds ratio < 1), identifying them as potential protective factors. Sensitivity analyses confirmed the absence of significant heterogeneity or horizontal pleiotr

Accelerated Aging in Cancer and Cancer Treatment: Current Status of Biomarkers.

BackgroundAging in humans is a heterogeneous process influenced by both biological and chronological factors. Biological age reflects an individual's physiological reserve and functional status. Increasing evidence suggests that cancer and its therapies accelerate biological aging. Many biomarkers have been evaluated to assess the biological age of patients with cancer. These biomarkers are emerging as potential tools to predict cancer-related toxicity and an individual's functional capacity as well as to individualize treatment.MethodsThis review summarizes the current literature on aging bio

The Potential Role of Proinflammatory Cytokines and Complement Components in the Development of Drug-Induced Neuropathy in Patients with Multiple Myeloma.

The launch of novel chemotherapeutic agents-in particular, proteasome inhibitors and immunomodulatory drugs-dramatically changed multiple myeloma (MM) therapy, improving the response rate and prolonging progression-free survival. However, none of the anti-MM drugs are deprived of side effects. Peripheral neuropathy (PN) seems to be one of the most pressing problems. Despite extensive research in this area, the pathogenesis of drug-induced peripheral neuropathy (DiPN) has not yet been fully elucidated. In the present study, we aimed to assess the potential relationship between proinflammatory f

Targeting Death Receptor 5 (DR5) for the imaging and treatment of primary bone and soft tissue tumors: an update of the literature.

BackgroundDeath Receptor 5 (DR5) is expressed on the surface of primary bone and soft tissue sarcoma cells, and its activation induces cell death primarily through apoptosis. The combination of DR5 agonists and commonly used chemotherapeutic agents, such as doxorubicin, can promote cell death. Currently, clinical trials are investigating the effectiveness of DR5 activation using new biological agents, such as bi-specific or tetravalent antibodies, in improving the survival of patients with relapsed or refractory cancers. Furthermore, investigations continue into the use of novel combination th

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

Анализ воздействия и реакции на белантамб мафодотин в сочетании с бортезомибами и дексаметазоном у пациентов с повторной/редактированной множественной миеломой из DREAM-6 Arm B и DREAM-7.

МАФОДОТИН, бортезомиб и дексаметасон (BVd) продемонстрировали клиническую активность в ходе этапа I/II DREAMM-6 (Арм B) и значительные клинические преимущества в ходе этапа III исследования DREAMM-7 для пациентов с повторной/реактивной множественной миеломой (RRMMM) и ≥1 предыдущей линии терапии. МЕТОДЫ: Для оценки зависимости между воздействием, эффективностью/безопасностью при различных дозах и графиками оценки рисков, связанных с выгодами, использовались белантамбовые мафодотины, полученные в результате фармакокинетического цикла 1 (C1).Результаты: Воздействие на Belantamab mafodotin C1 был

Resveratrol from Dietary Supplement to a Drug Candidate: An Assessment of Potential.

Resveratrol (RVT) is a well known phyto-chemical and is widely used in dietary supplements and botanical products. It shows a wide range of pharmacological/beneficial effects. Therefore, it can be a potential candidate to be developed as phyto-pharmaceutical. Multiple diseases are reported to be treated by the therapeutic effect of RVT since it has antioxidant, anti-cancer activity and anti-inflammatory activities. It also has a major role in diabetes, arthritis, cardiac disorder and platelet aggregation etc. The major requirements are establishments regarding safety, efficacy profile and phys

A systematic literature review of the efficacy, effectiveness, and safety of filgrastim.

PurposeFilgrastim (NEUPOGEN®) is the originator recombinant human granulocyte colony-stimulating factor widely used for preventing neutropenia-related infections and mobilizing hematopoietic stem cells. This report presents findings of a systematic literature review and meta-analysis of efficacy and safety of originator filgrastim to update previous reports.MethodsA literature search of electronic databases, congress abstracts, and bibliographies of recent reviews was conducted to identify English-language reports of clinical trials and observational studies evaluating filgrastim in its US-app

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

New agents in the Treatment of Myeloma Bone Disease.

Patients with multiple myeloma develop a devastating bone disease driven by the uncoupling of bone remodelling, excess osteoclastic bone resorption and diminished osteoblastic bone formation. The bone phenotype is typified by focal osteolytic lesions leading to pathological fractures, hypercalcaemia and other catastrophic bone events such as spinal cord compression. This causes bone pain, impaired functional status, decreased quality of life and increased mortality. Early in the disease, malignant plasma cells occupy a niche environment that encompasses their interaction with other key cellula

Curcumin and Its Derivatives as Anticancer Agents in Head and Neck Cancer: Molecular Mechanisms and Preclinical Evidence

Head and neck cancer (HNC), particularly oral squamous cell carcinoma (OSCC), remains a major clinical challenge due to its aggressive behavior, high recurrence rates, and frequent resistance to conventional therapies. Natural compounds, especially curcumin and its derivatives, have gained increasing attention as potential anticancer agents due to their ability to target multiple molecular pathways involved in tumor progression. This review critically evaluates the current preclinical and translational evidence supporting curcumin and its derivatives as monotherapeutic agents in HNC, with part

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… Curcumin induced cell-cycle arrest at the G0/G1 phase and downregulated the expression of hypoxia- and angiogenesis-related genes, such as STAT3, MMP-3, VEGF, and HIF-1α. Molecular docking analysis showed that of the genes evaluated, curcumin had the highest affinity with MMP-3 [ 189 ]. …

The Potential of Nuclear Pore Complexes in Cancer Therapy.

Nuclear pore complexes (NPCs) play a critical role in regulating transport-dependent gene expression, influencing various stages of cancer development and progression. Dysregulation of nucleocytoplasmic transport has profound implications, particularly in the context of cancer-associated protein mislocalization. This review provides specific information about the relationship between nuclear pore complexes, key regulatory proteins, and their impact on cancer biology. Highlighting the influence of tumor-suppressor proteins as well as the potential of gold nanoparticles and intelligent nanosyste

Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma.

Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub