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Boosting Immunity against Multiple Myeloma.

Despite the improvement of patient's outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody-drug conjugates or bispecific antibodies broadened the possibility of improving patients' survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residua

TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches.

TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent a biologically and clinically distinct subset of myeloid malignancies characterized by poor prognosis, resistance to standard therapies, and high rates of relapse. TP53 mutations, particularly biallelic are frequently associated with complex karyotypes and confer profound chemoresistance. Although hypomethylating agents and venetoclax-based combinations provide modest benefit, durable remissions remain rare. Novel therapeutic strategies targeting mutant p53, restoring wild-type function, or exploiting synth

Genomic profiling enables personalized strategies to overcome drug resistance in multiple myeloma.

Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. It is a complex and heterogeneous disease that primarily affects older adults and is associated with significant morbidity and mortality. Despite advances in treatment, including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, MM remains largely incurable, with most patients experiencing relapse and disease progression. The disease’s biological complexity is driven by a multitude of genetic and molecular alterations, which contr

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… Typical consolidation regimens mirror induction (for example 2–4 cycles of bortezomib/lenalidomide/dexamethasone or bortezomib-based triplets) and have shown improvements in depth of response and progression-free survival in several trials (e.g., EMN02/HOVON95 and other studies), although the OS benefit …

Tyrosine Kinase Inhibitors, Antibody-Drug Conjugates, and Bispecific Antibodies in Oncogene-Driven Non-Small-Cell Lung Cancer: Evolving Roles in Treatment Sequencing and Resistance Management.

The treatment landscape of oncogene-driven non-small-cell lung cancer (NSCLC) has evolved substantially with the development of targeted therapies directed against actionable molecular alterations. Tyrosine kinase inhibitors (TKIs) remain the cornerstone of treatment for many driver-defined subsets; however, acquired resistance, central nervous system progression, and tumor heterogeneity continue to limit long-term disease control. This review examines the mechanistic foundations, clinical evidence, resistance patterns, and emerging therapeutic roles of TKIs, antibody-drug conjugates (ADCs), a

Синдром PEEMS: 2026 Обновленная информация по диагностике, статистике рисков и управлению.

Синдром PEMS — это угрожающий жизни синдром, вызванный плазменной неоплазмой. Основными критериями для этого синдрома являются полиномропатическое расстройство клональных клеток (ПХД), склеротические повреждения костей, повышенный сосудистый эндотелиальный фактор роста и наличие болезни Каслмана. Незначительные особенности включают в себя органомегалию, эндокринопатию, характерные изменения кожи, папилледему, вневаскулярную перегрузку объема и тромбоцитоз. Диагноз синдрома POEMS three основных критериев, two в том числе полиномропаты и клональные плазменные клетки, и по крайней мере one незнач

Advances in nanotechnology-enabled adjuvants for peptide-based cancer vaccines.

Peptide-based vaccines only contain peptide epitopes and exclude unnecessary biological materials, which greatly reduces the risk of causing an undesired immune response and further improves the safety profile, garnering considerable interest in vaccine development. However, the immunogenicity induced by these peptides alone is not potent enough to elicit an effective immune response. Recently, combining the adjuvants with peptide antigens has shown promising effects to realize a satisfying immune response. In this review, we discuss the development of immunoadjuvants to enhance the safety and

Emerging Targets in Non-Small Cell Lung Cancer.

Lung cancer is responsible for a high burden of disease globally. Over the last two decades, the discovery of targetable oncogenic genomic alterations has revolutionized the treatment landscape for early-stage and advanced non-small cell lung cancer (NSCLC). New molecular drivers continue to emerge as promising therapeutic targets, including KRAS non-G12C, RAF/MEK, HER3, Nectin-4, folate receptor alpha, ITGB6, and PRMT5. In this review, we summarize the emerging molecular targets with a potential clinical impact in advanced NSCLC, elaborating on their clinical characteristics and specific mech

Frailty as an Effect Modifier in Randomized Controlled Trials: A Systematic Review.

BackgroundThe effect of clinical interventions may vary by patients' frailty status. Understanding treatment effect heterogeneity by frailty could lead to frailty-guided treatment strategies and reduce overtreatment and undertreatment. This systematic review aimed to examine the effect modification by frailty in randomized controlled trials (RCTs) that evaluate pharmacological, non-pharmacological, and multicomponent interventions.MethodsWe searched PubMed, Web of Science, EMBASE, and ClinicalTrial.gov, from their inception to 8 December 2023. Two reviewers independently extracted trial data a

Myeloma Bone Disease: A Comprehensive Review.

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells in the bone marrow microenvironment, characterized by overproduction of heavy- and light-chain monoclonal proteins (M-protein). These proteins are mainly found in the serum and/or urine. Reduction in normal gammaglobulins (immunoparesis) leads to an increased risk of infection. The primary site of origin is the bone marrow for nearly all patients affected by MM with disseminated marrow involvement in most cases. MM is known to involve bones and result in myeloma bone disease. Osteolytic lesions are seen in 80% of patien

CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool.

Bacteriophages are pervasive viruses that infect bacteria, relying on their genetic machinery to replicate. In order to protect themselves from this kind of invader, bacteria developed an ingenious adaptive defence system, clustered regularly interspaced short palindromic repeats (CRISPR). Researchers soon realised that a specific type of CRISPR system, CRISPR-Cas9, could be modified into a simple and efficient genetic engineering technology, with several improvements over currently used systems. This discovery set in motion a revolution in genetics, with new and improved CRISPR systems being

T-cell engagers in cancer immunotherapy: mechanisms, challenges, and future perspectives.

T-cell engagers (TCEs) are a rapidly evolving class of cancer immunotherapies that redirect cytotoxic T cells to tumor-associated antigens independently of MHC presentation. This review outlines the development, structural formats, and therapeutic potential of various TCE platforms, including bispecific (BiTEs) and trispecific T-cell engagers (TriTEs), dual affinity re-targeting (DART), and other emerging formats. We also highlight the clinical success in treating hematologic malignancies as demonstrated by agents such as blinatumomab and teclistamab. We also discussed the ongoing challenges i

Systematic review of patient-reported outcome item libraries in cancer research: an EORTC Quality of Life Group study.

BackgroundPatient-reported outcome (PRO) item libraries support flexible PRO assessment in cancer research by facilitating the development of customized item lists. However, little is known about the use of item lists in clinical research. This systematic review addresses this by assessing utilization of PRO item libraries and lists in oncology research.MethodsA systematic review of MEDLINE, Embase, and CINAHL identified cancer studies using PRO item libraries to develop item lists, regardless of study design, published between October 2021 and September 2025. Key features of item library usag

Applications of Aggregation-Induced Emission Materials in Immunology: From Diagnostics to Immunotherapy.

Aggregation-induced emission (AIE) materials, due to their unique ability to significantly enhance optical emission in aggregated states, have demonstrated vast potential in immunology, particularly in early disease diagnosis and immunotherapy. AIE materials can serve as highly efficient fluorescent probes for biomarker detection, providing critical insights for early diagnosis. Additionally, they can act as cancer vaccines, enhancing the effectiveness of immunotherapy through photodynamic therapy, photothermal therapy, or activation of immune cells. This review highlights the applications of

Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment.

Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard "one size fits all"

Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer.

Prostate cancer (PC) is the second most common cancer in men worldwide. More than 65% of men diagnosed with PC are above 65. Patients with localized PC show high long-term survival, however with the disease progression into a metastatic form, it becomes incurable, even after strong radio- and/or chemotherapy. Sphingosine 1-phosphate (S1P) is a bioactive lipid that participates in all the steps of oncogenesis including tumor cell proliferation, survival, migration, invasion, and metastatic spread. The S1P-producing enzymes sphingosine kinases 1 and 2 (SK1 and SK2), and the S1P degrading enzyme

Recent Advances in the Applications of Small Molecules in the Treatment of Multiple Myeloma.

Therapy for multiple myeloma (MM), a hematologic neoplasm of plasma cells, has undergone remarkable changes over the past 25 years. Small molecules (molecular weight of less than one kDa), together with newer immunotherapies that include monoclonal antibodies, antibody-drug conjugates, and most recently, chimeric antigen receptor (CAR) T-cells, have combined to double the disease's five-year survival rate to over 50% during the past few decades. Despite these advances, the disease is still considered incurable, and its treatment continues to pose substantial challenges, since therapeutic refra

Role of Next Generation Immune Checkpoint Inhibitor (ICI) Therapy in Philadelphia Negative Classic Myeloproliferative Neoplasm (MPN): Review of the Literature.

The Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are enduring and well-known conditions. These disorders are characterized by the abnormal growth of one or more hematopoietic cell lineages in the body's stem cells, leading to the enlargement of organs and the manifestation of constitutional symptoms. Numerous studies have provided evidence indicating that the pathogenesis of these diseases involves the dysregulation of the immune system and the presence of chronic inflam

The Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of acute leukemia.

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment

Какие поведенческие, эмоциональные и школьные проблемы в средней школе предсказывают раннее сексуальное поведение?

Считается, что проблемы с психическим здоровьем и корректировкой школ отличают раннее сексуальное поведение от нормативных сроков (см.16-18 ), но мало что известно о том, как ранние сексуальные отношения возникают из-за этих проблем среднего возраста. Существующие исследования не допускают сопутствующих проблем, различий в наступлении и стойкости, и нет никакой информации о корректировке средней школы в связи с ранними половыми отношениями. В этом исследовании изучалась связь между несколькими проблемами среднего возраста и ранним сексуальным поведением с использованием подвыборки (N = 4,739,

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… Second-born twins, triplets and quadruplets were excluded from this study. …

Clinical applications of antibody-drug conjugates in advanced non-small cell lung cancer.

Lung cancer remains the leading cause of cancer-related incidence and mortality worldwide, with non-small cell lung cancer (NSCLC) constituting the majority of cases. Current treatment modalities are constrained by significant limitations: conventional chemotherapy exhibits poor tumor selectivity and systemic toxicity, while monoclonal antibodies frequently demonstrate inadequate therapeutic efficacy. Antibody-drug conjugates (ADCs)-engineered biotherapeutics comprising tumor-targeting antibodies conjugated to potent cytotoxic agents through optimized linkers-have emerged as a transformative s