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Bispecific and multispecific immune engagers for redirecting innate and adaptive immunity against hematologic cancers.

Bispecific antibodies (BsAbs) and multispecific antibodies (MsAbs) represent a transformative class of immunotherapeutics in oncology. These engineered molecules possess the unique ability to simultaneously target two or more distinct antigens, thereby facilitating precise immune cell engagement and disrupting multiple signaling pathways. This comprehensive review focuses on their pivotal role in redirecting both innate (natural killer cells, phagocytes) and adaptive (T cells) immunity, with a particular emphasis on their application against hematologic cancers. Significant clinical successes,

Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma.

The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progre

Taming renal inflammation: signaling pathways and therapeutic advances in lupus nephritis.

Lupus nephritis (LN), a serious complication of systemic lupus erythematosus (SLE), involves complex immune dysregulation that leads to chronic renal inflammation and progressive tissue damage. Despite decades of use of standard immunosuppressive therapy, treatment responses remain variable, and many patients experience relapses or develop end-stage renal disease. This review synthesizes emerging insights into the immunopathogenesis of LN, drawing on studies from single-cell transcriptomics, signaling pathway analyses and renal tissue immunology. It examines the role of both innate and adaptiv

Wnt/β-catenin signaling pathway: proteins' roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis.

Osteoblasts are mainly derived from mesenchymal stem cells in the bone marrow. These stem cells can differentiate into osteoblasts, which have the functions of secreting bone matrix, promoting bone formation, and participating in bone remodeling. The abnormality of osteoblasts can cause a variety of bone-related diseases, including osteoporosis, delayed fracture healing, and skeletal deformities. In recent years, with the side effects caused by the application of PTH drugs, biphosphonate drugs, and calmodulin drugs, people have carried out more in-depth research on the mechanism of osteoblast

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Prevalence of symptomatic toxicities for novel therapies in adult oncology trials: a scoping review.

BackgroundPatients' self-report of their symptoms can provide important data for the evaluation of treatment benefit and tolerability of oncology drugs. Contemporary treatment approaches, including immunotherapy and molecular targeted therapies, have unique toxicities based on their novel mechanisms of action. This scoping review aimed to summarize evidence from existing reviews and clinical practice guidelines to examine the type and prevalence of toxicities including symptomatic adverse events (sympAEs) for adult cancer patients to inform clinical care and therapeutic trials.MethodsA systema

Exosomes: innovative biomarkers leading the charge in non-invasive cancer diagnostics.

Exosomes, nanoscale extracellular vesicles secreted by diverse cell types, have emerged as promising biomarkers for non-invasive tumor diagnostics, offering significant advantages over traditional methods. These vesicles, typically ranging from 30 to 150 nanometers in size, carry a diverse cargo of proteins, lipids, RNA, and microRNAs, which reflect the molecular alterations occurring within their parent cells. Notably, exosomes can be isolated from easily accessible biofluids such as blood, urine, and saliva, making them ideal candidates for liquid biopsy applications. This review explores th

2023 Scientific Session of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), Montréal, Canada, 19 March–April 1 2023: Posters

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ISEV2019 Abstract Book

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.

Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in

Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.

The increasing global burden of cancer necessitates innovative therapeutic strategies. Cell therapy represents a major breakthrough in oncology, evolving rapidly from the successful application of chimeric antigen receptor T (CAR-T) cells in hematologic malignancies to a multiplatform landscape characterized by the concurrent development of diverse strategies. Current research focuses on T cell receptor-engineered T (TCR-T) cells, tumor-infiltrating lymphocytes (TILs), gamma delta (γδ) T cells, CAR-natural killer (CAR-NK) cells, CAR-macrophages (CAR-Ms), and various strategies based on dendrit

Antibody-drug conjugates in cancer therapy: current advances and prospects for breakthroughs.

Antibody-drug conjugates (ADCs), often referred to as "intelligent biological missiles," have garnered significant attention in the rapidly evolving landscape of cancer therapy. ADCs represent a sophisticated approach by integrating monoclonal antibodies (mAbs), which are particular targeting tumor antigens, with cytotoxic payloads, which deliver lethal effects. Compared with the combination of chemotherapy and mAbs, ADCs precisely deliver highly potent cytotoxins directly to tumor cells while minimizing damage to healthy tissues. However, limitations such as significant adverse effects, subop

Cardiac Monitoring for Patients Undergoing Treatment With MEK Inhibitor Monotherapy.

PURPOSE OF REVIEW: Aberrant activation of the RAS-RAF-MEK-ERK signaling pathway contributes to numerous malignancies, congenital syndromes, and cardiovascular disorders, establishing MEK inhibitors (MEKi) as crucial therapeutic agents. MEKi demonstrate substantial clinical benefit as monotherapy (e.g., NF1-associated tumors) or combination therapy (e.g., melanoma, glioma, congenital RASopathies). Cardiovascular adverse events, primarily asymptomatic reductions in left ventricular ejection fraction (LVEF), have prompted intensive echocardiographic monitoring. RECENT FINDINGS: Emerging evidence

Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: a randomized, open-label, multicenter, phase 2 study (CENTAURUS).

Current guidelines for smoldering multiple myeloma (SMM) recommend active monitoring until the onset of multiple myeloma (MM) before initiating treatment or enrollment in a clinical trial. Earlier intervention may delay progression to MM. In CENTAURUS, 123 patients with intermediate-risk or high-risk SMM were randomly assigned to daratumumab 16 mg/kg intravenously on extended intense (intense), extended intermediate (intermediate), or short dosing schedules. At the prespecified primary analysis (15.8-month median follow-up), the complete response (CR) rates (co-primary endpoint) were 2.4%, 4.9

Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors.

In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. Compared with cytotoxic T lymphocytes, NK cells take a unique position targeting tumor cells that evade the host immune surveillance by down-regulating self-antigen presentation. Recent findings highlighted that NK cells can even target cancer stem cells. The efficacy of allogeneic NK cells has been widely investigated in the treatment of hematologic malignancies. In solid tumors, both autologous and allogeneic NK cells have demonstrated potential efficacy. In allogeneic

The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies.

Immunotherapy has emerged as a preeminent force in the domain of cancer therapeutics and achieved remarkable breakthroughs. Nevertheless, the high resistance has become the most substantial impediment restricting its clinical efficacy. Beta-2 microglobulin (B2M), the light chain of major histocompatibility complex (MHC) class I, plays an indispensable part by presenting tumor antigens to cytotoxic T lymphocytes (CTLs) for exerting anti-tumor effects. Accumulating evidence indicates that B2M mutation/defect is one of the key mechanisms underlying tumor immunotherapy resistance. Therefore, eluci

Lymphangioleiomyomatosis and Pregnancy-Do We Have All the Answers for a Woman Who Desires to Conceive?-Literature Review.

Lymphangioleiomyomatosis (LAM) is a rare, progressive, and poor-prognosis systemic disorder that primarily affects women of reproductive age, with a higher prevalence among individuals of Caucasian origin. However, there are limited reliable data on the prevalence of LAM during pregnancy. The fulminant respiratory clinical presentation that often includes progressive dyspnea on exertion, cough, or hemoptysis, frequently complicated by pneumothorax, and the increased risk of spontaneous abortion due to increased estrogen and progesterone production during gestation, are arguments that most ofte

Novel Molecular Therapies and Genetic Landscape in Selected Rare Diseases with Hematologic Manifestations: A Review of the Literature.

Rare diseases affect less than 1 in 2000 people and are characterized by a serious, chronic, and progressive course. Among the described diseases, a mutation in a single gene caused mastocytosis, thrombotic thrombocytopenic purpura, Gaucher disease, and paroxysmal nocturnal hemoglobinuria (KIT, ADAMTS13, GBA1, and PIG-A genes, respectively). In Castleman disease, improper ETS1, PTPN6, TGFBR2, DNMT3A, and PDGFRB genes cause the appearance of symptoms. In histiocytosis, several mutation variants are described: BRAF, MAP2K1, MAP3K1, ARAF, ERBB3, NRAS, KRAS, PICK1, PIK3R2, and PIK3CA. Genes like H

Targeting the JAK2/STAT3 Pathway-Can We Compare It to the Two Faces of the God Janus?

Muscle cachexia is one of the most critical unmet medical needs. Identifying the molecular background of cancer-induced muscle loss revealed a promising possibility of new therapeutic targets and new drug development. In this review, we will define the signal transducer and activator of transcription 3 (STAT3) protein's role in the tumor formation process and summarize the role of STAT3 in skeletal muscle cachexia. Finally, we will discuss a vast therapeutic potential for the STAT3-inhibiting single-agent treatment innovation that, as the desired outcome, could block tumor growth and generally

Update of early phase clinical trials in cancer immunotherapy.

Immunotherapy has revolutionized the landscape of cancer treatment and become a standard pillar of the treatment. The two main drivers, immune checkpoint inhibitors and chimeric antigen receptor T cells, contributed to this unprecedented success. However, despite the striking clinical improvements, most patients still suffer from disease progression because of the evolution of primary or acquired resistance. This mini-review summarizes new treatment options including novel targets and interesting combinational approaches to increase our understanding of the mechanisms of the action of and resi

Mesenchymal Stromal Cells: Bridging the Gaps in Hematologic Disease Therapy.

Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in hematologic diseases by modulating immune responses, supporting hematopoiesis, and remodeling the bone marrow microenvironment. Clinically, MSCs have been explored for graft-versus-host disease and hematopoietic stem cell transplantation support, while their applications in hematologic malignancies, including acute myeloid leukemia, multiple myeloma, and myelodysplastic syndromes, remain under investigation. However, therapeutic heterogeneity, safety concerns, and standardization challenges limit their clinical transla