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Post-marketing safety of tarlatamab in small cell lung cancer based on FAERS and WHO-VigiAccess with SHAP-based interpretable machine learning analysis of immune-related adverse events.

BACKGROUND: Tarlatamab is a DLL3-targeted bispecific T-cell engager approved for previously treated extensive-stage small cell lung cancer (ES-SCLC). However, its post-marketing safety profile in routine practice remains incompletely characterized. METHODS: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System from Q2 2024 to Q3 2025, with a descriptive cross-database comparison using WHO-VigiAccess. Disproportionality analyses were performed using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, an

Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening.

Molecular targeted therapy has revolutionized the landscape of cancer treatment due to better therapeutic responses and less systemic toxicity. However, therapeutic resistance is a major challenge in clinical settings that hinders continuous clinical benefits for cancer patients. In this regard, unraveling the mechanisms of drug resistance may identify new druggable genetic alterations for molecularly targeted therapies, thus contributing to improved therapeutic efficacies. The recent rapid development of novel methodologies including CRISPR-Cas9 screening technology and patient-derived models

Dual regulation of gastrointestinal tumor progression by the IFN-γ/STAT1 pathway and prospects for targeted therapy.

Gastrointestinal malignant tumors exhibit a high incidence and mortality rate among all malignancies worldwide, making them a significant concern within the field of oncology. Targeted therapy for gastrointestinal tumors has become a hot topic in recent years, and its specific mechanism remains to be further elucidated. Secreted factors, including cytokines, chemokines, and growth factors, as components of the tumor microenvironment, play a crucial role in the progression of gastrointestinal tumors. Interferon-gamma (IFN-γ) can activate these factors through JAK1/2 and STAT1 signaling (the IFN

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… Some studies have suggested that this may be related to the mobilization of response to endothelial progenitor cells ( 86 ). It remains unclear whether the IFN-γ/STAT1 signaling regulates the immune escape for tumor progression demonstrated here by CXCL10/CXCR3. …

"Bioinspired" Membrane-Coated Nanosystems in Cancer Theranostics: A Comprehensive Review.

Achieving precise cancer theranostics necessitates the rational design of smart nanosystems that ensure high biological safety and minimize non-specific interactions with normal tissues. In this regard, "bioinspired" membrane-coated nanosystems have emerged as a promising approach, providing a versatile platform for the development of next-generation smart nanosystems. This review article presents an in-depth investigation into the potential of these nanosystems for targeted cancer theranostics, encompassing key aspects such as cell membrane sources, isolation techniques, nanoparticle core sel

A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of cli

Молекулярные модели, связанные с ущербом от митохондриала: нейроиммуномодуляторы в патофизиологии центральной нервной системы.

Нейроинфламмация способствует широкому спектру нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Его движут неевропейские глиальные клетки, главным образом микроглии и астроциты. Микроглии являются постоянными иммунными клетками центральной нервной системы, в то время как астроциты являются основными элементами поддержки нейронных функций, но могут также участвовать в нейроиммунной реакции. Оба этих типа глиальных клеток могут стать реактивными при обнаружении определенных внутриклеточных молекул, которые появляются в

Advances in improving cancer immunotherapy with nanotechnology: from smart nanoparticles to synergistic combination strategies.

Cancer immunotherapy has substantially advanced cancer treatment, achieving durable responses in select malignancies. However, its widespread application is limited by significant challenges: low efficacy in many solid tumors, severe side effects, and immune evasion facilitated by the tumor microenvironment (TME). Nanotechnology offers a promising approach to address these obstacles. By employing nanoparticles (NPs), we can precisely deliver therapeutics to tumor sites, ensure controlled release to minimize side effects, and amplify the immune response, thereby substantially boosting the effec

CAR T-клеточная терапия в раковых заболеваниях: учет перспектив ухода за больными в целях улучшения ухода за больными.

Цимерная антигенная рецепторная (CAR) T-клетотерапия представляет собой значительный прогресс в лечении рака, особенно в случае гематологовых магнестов. В настоящее время изучаются различные стратегии иммунотерапии рака, включая цитокины, вакцины от рака, ингибиторы иммунной системы, иммуномодуляторы моноклонных антител и т.д. Эта терапия продемонстрировала впечатляющую эффективность в лечении таких заболеваний, как острая лимфоболическая лейкемия (АЛЛ), диффузная большая лимфома B-клеток (DLBCL) и миелома, часто приводящая к полной ремиссии в рефрактных случаях. Вместе с тем клиническое приме

Aplidin (plitidepsin) is a novel anti-myeloma agent with potent anti-resorptive activity mediated by direct effects on osteoclasts.

Despite recent progress in its treatment, Multiple Myeloma (MM) remains incurable and its associated bone disease persists even after complete remission. Thus, identification of new therapeutic agents that simultaneously suppress MM growth and protect bone is an unmet need. Herein, we examined the effects of Aplidin, a novel anti-cancer marine-derived compound, on MM and bone cells. In vitro, Aplidin potently inhibited MM cell growth and induced apoptosis, effects that were enhanced by dexamethasone (Dex) and bortezomib (Btz). Aplidin modestly reduced osteocyte/osteoblast viability and decreas

Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predic

MicroRNAs in Aseptic Loosening of Prosthesis: Pathophysiology and Potential Therapeutic Approaches.

OBJECTIVES: Aseptic loosening (AL) is one of the leading causes of total joint arthroplasty (TJA) revision. Discovering the roles of microRNAs (miRNA/miR) in ontogenesis and osteolysis has attracted more attention to diagnosing and treating bone disorders. This review aimed to summarize miRNA biogenesis and describe the involvement of miRNAs in AL of implants. METHODS: A detailed search was carried out on scientific search engines, including Google Scholar, Web of Science, and PubMed, to find appropriate papers related to subjects. The search process was performed using the following keywords

Spotlight on Melphalan Flufenamide: An Up-and-Coming Therapy for the Treatment of Myeloma.

Despite recent therapeutic advances, multiple myeloma (MM) patients experience relapses as they become resistant to various classes and combinations of treatment. Melphalan (L-PAM) is an ageless drug. However, its use in the autologous stem cell transplantation (ASCT) setting and the innovative quadruplet regimen as well as daratumumab, bortezomib, and prednisone make this old drug current yet. Melflufen is a peptide-conjugated alkylator belonging to a novel class of compounds, representing an overcoming of L-PAM in terms of mechanism of action and effectiveness. The improved melflufen cytotox

Mesenchymal stem/stromal cells in cancer therapy.

The multipotent mesenchymal stem/stromal cells (MSCs), initially discovered from bone marrow in 1976, have been identified in nearly all tissues of human body now. The multipotency of MSCs allows them to give rise to osteocytes, chondrocytes, adipocytes, and other lineages. Moreover, armed with the immunomodulation capacity and tumor-homing property, MSCs are of special relevance for cell-based therapies in the treatment of cancer. However, hampered by lack of knowledge about the controversial roles that MSC plays in the crosstalk with tumors, limited progress has been made with regard to tran

Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential.

Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic

Кинуреньенс и митохондриальные расстройства в многоразовом склерозе.

Множественный склероз (MS) — хроническое аутоиммунное заболевание, характеризующееся воспалением, обезвоживанием и нейродегенерацией в центральной нервной системе. Патогенез MS связан с иммунной атаки на миелин и нейроны, сопровождаемой дисфункцией мозга в крови и хроническим воспалением CNS. Центральное значение для патологии MS имеет дисрегулирование кинуреньинового пути, который метаболизирует триптофан в нейроактивные соединения. Активация Kynurenin Translation (KP) под воздействием подстрекательских цитокинов приводит к образованию как нейрозащитных (например, кинуриновой кислоты, КИНА),

The Roadmap of RANKL/RANK Pathway in Cancer.

The receptor activator of the nuclear factor-κB ligand (RANKL)/RANK signaling pathway was identified in the late 1990s and is the key mediator of bone remodeling. Targeting RANKL with the antibody denosumab is part of the standard of care for bone loss diseases, including bone metastases (BM). Over the last decade, evidence has implicated RANKL/RANK pathway in hormone and HER2-driven breast carcinogenesis and in the acquisition of molecular and phenotypic traits associated with breast cancer (BCa) aggressiveness and poor prognosis. This marked a new era in the research of the therapeutic use o

The Emerging Role of the FGF/FGFR Pathway in Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumors (GIST) are rare neoplasms of mesenchymal origin arising in the gastrointestinal tract. The vast majority are characterized by mutually exclusive activating mutations in KIT or Platelet-derived growth factor alpha (PDGFRA) receptors, or less frequently by succinate dehydrogenase complex (SDH) or NF1 inactivation, with very rare cases harboring mutant BRAF or RAS alleles. Approximately 5% of GISTs lack any of such mutations and are called quadruple wild-type (WT) GISTs. Recently, deregulated Fibroblast Growth Factor (FGF)/FGF-receptor (FGFR) signaling emerged as a

Tumor Whole-Genome Sequencing for Prediction of Venous Thromboembolism in Patients With Metastasized Solid Cancer.

BACKGROUND: International guidelines suggest prophylactic anticoagulation for patients with cancer at high risk of venous thromboembolism (VTE). Here, we evaluated whether tumor whole-genome sequencing data may improve the selection of high-risk patients. METHODS: In a pan-cancer cohort of 3087 patients, associations of candidate clinical predictors, the germline extended 297-single nucleotide polymorphism polygenic risk score, tumor mutational characteristics, and somatic tumor mutations with VTE were estimated by calculating hazard ratios (HRs). RESULTS: During 12-month follow-up, 237 (7.7

Burden of Disease, Treatment Patterns, and Healthcare Resource Utilization in Multiple Myeloma in the Middle East and North Africa Region: A Targeted Literature Review.

Globally, the multiple myeloma (MM) landscape varies widely, with incidence, treatment patterns, outcomes, and healthcare resource utilization (HCRU) differing across countries and regions. Many factors contribute to these differences, including ethnicity, awareness, and socioeconomic influences. This is the first analysis aiming to explore factors associated with myeloma incidence and patient characteristics in the Middle East and North Africa (MENA) region. A literature search was conducted using PubMed and Embase from 1 January 2015 to 30 May 2025. Articles reporting outcomes of interest in

Иммунитет в нейромодуляции: исследование нейронных и иммунных путей в расстройствах мозга.

Иммунитет четко регулирует функцию мозга. Она непосредственно участвует в патологических процессах таких нейродегенеративных заболеваний, как болезнь Паркинсона и Альцгеймера, посттравматические заболевания, множественный склероз, травма головного мозга и психические расстройства (большое расстройство организма, серьезное депрессивное расстройство (МДС), расстройства тревожности, расстройства психоза и шизофрения, а также расстройства нервного развития (НРД). Нейромодулирование в настоящее время является одной из ведущих терапевтических стратегий лечения этих расстройств, однако пока мало что