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The beginning of a new therapeutic era in acute myeloid leukemia.

In the field of AML, the early 2000s were shaped by the advent of novel molecular biology technologies including high-throughput sequencing that improved prognostic classification, response evaluation through the quantification of minimal residual disease, and the launch of research on targeted therapies. Our knowledge of leukemogenesis, AML genetic diversity, gene-gene interactions, clonal evolution, and treatment response assessment has also greatly improved. New classifications based on chromosomal abnormalities and gene mutations are now integrated on a routine basis. These considerable ef

Epigenetic drugs in cancer therapy: mechanisms, immune modulation, and therapeutic applications.

Epigenetic regulation is a fundamental mechanism controlling gene expression and cellular function, primarily mediated through reversible modifications such as DNA methylation, histone acetylation, and chromatin remodeling. Dysregulation of critical epigenetic enzymes, including histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and bromodomain and extraterminal domain (BET) proteins, has been closely associated with tumor initiation, progression, metastasis, immune evasion, and resistance to conventional therapies. Targeting these epigenetic regulators with small-molecule inhibitor

Recent Progress of CircRNAs in Hematological Malignancies.

Circular RNAs (circRNAs) are now recognized as key regulators in the epigenetic control of genetic expression, being involved in a wide range of cellular activities such as proliferation, differentiation, and apoptosis. Their unique closed-loop structure endows them with stability and resistance to exonuclease degradation, making them not only key regulatory molecules within the cell but also promising biomarkers for disease diagnosis and prognosis, particularly in hematological malignancies. This review comprehensively explores the role of circRNAs in the pathogenesis, progression, and therap

Neurofilament light chain in serum of cancer patients with acute neurological complications.

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelit

The treatment landscape in thyroid cancer: a focus on cabozantinib.

Although patients with thyroid cancer generally fare well, there is a subset for which this is not necessarily true. Progress in understanding the molecular aberrations in thyroid cancer has led to a change in the management of these cases. Since 2011, four multikinase inhibitors (MKIs) have been approved by the US Food and Drug Administration for thyroid cancer - cabozantinib and vandetanib for medullary thyroid cancer and sorafenib and lenvatinib for differentiated thyroid cancer. This change in the treatment landscape has raised challenges for practitioners who may not be familiar with the

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… These include alterations in genes such as EIF1AX (eukaryotic translation initiation factor 1A, X-linked), PPM1D (protein phosphatase, Mg 2+ /Mn 2+ dependent, 1D), and CHEK2 (checkpoint kinase 2). …

Applications of nanotechnologies for miRNA-based cancer therapeutics: current advances and future perspectives.

MicroRNAs (miRNAs) are short (18-25 nt), non-coding, widely conserved RNA molecules responsible for regulating gene expression via sequence-specific post-transcriptional mechanisms. Since the human miRNA transcriptome regulates the expression of a number of tumor suppressors and oncogenes, its dysregulation is associated with the clinical onset of different types of cancer. Despite the fact that numerous therapeutic approaches have been designed in recent years to treat cancer, the complexity of the disease manifested by each patient has prevented the development of a highly effective disease

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… As a result, miR-181a directly bound to the transcripts of its target gene RAD17 checkpoint clamp loader component ( RAD17 ), responsible for regulating checkpoint kinase 2 (Chk2) pathway, causing RAD17 downregulation in radioresistant cells and the overexpression of Chk2 protein ( Zhou et al., 2021 …

A Comprehensive Biological and Clinical Perspective Can Drive a Patient-Tailored Approach to Multiple Myeloma: Bridging the Gaps between the Plasma Cell and the Neoplastic Niche.

There is a broad spectrum of diseases labeled as multiple myeloma (MM). This is due not only to the composite prognostic risk factors leading to different clinical outcomes and responses to treatments but also to the composite tumor microenvironment that is involved in a vicious cycle with the MM plasma cells. New therapeutic strategies have improved MM patients' chances of survival. Nevertheless, certain patients' subgroups have a particularly unfavorable prognosis. Biological stratification can be subdivided into patient, disease, or therapy-related factors. Alternatively, the biological sig

Viral Vector-Based Melanoma Gene Therapy.

Gene therapy applications of oncolytic viruses represent an attractive alternative for cancer treatment. A broad range of oncolytic viruses, including adenoviruses, adeno-associated viruses, alphaviruses, herpes simplex viruses, retroviruses, lentiviruses, rhabdoviruses, reoviruses, measles virus, Newcastle disease virus, picornaviruses and poxviruses, have been used in diverse preclinical and clinical studies for the treatment of various diseases, including colon, head-and-neck, prostate and breast cancer as well as squamous cell carcinoma and glioma. The majority of studies have focused on i

Unveiling the Synergistic Potential: Bispecific Antibodies in Conjunction with Chemotherapy for Advanced Non-Small-Cell Lung Cancer Treatment.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of the cases. Despite advancements in targeted therapies and immunotherapies, many patients still rely on chemotherapy, highlighting the need for innovative treatment strategies. Bispecific antibodies (bsAbs), which feature two distinct binding sites capable of targeting different antigens, have emerged as a promising therapeutic approach, particularly in combination with chemotherapy. This review explores the scientific evolution and clinical applica

Rare central nervous system lymphomas.

Central nervous system (CNS) lymphomas are rare malignancies characterised by lymphoid infiltration into the brain, spinal cord, cranial nerves, meninges and/or eyes in the presence or absence of previous or concurrent systemic disease. Most CNS lymphomas are of the diffuse large B-cell lymphoma (DLBCL) subtype for which treatment strategies, particularly the use of high-dose methotrexate-based protocols and consolidation with autologous stem cell transplantation, are well established. Other histopathological subtypes of CNS lymphoma are comparatively less common with published data on these r

The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic three-dimensional renal tumouroids.

Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia

Combined inhibition of JAK1,2/Stat3‑PD‑L1 signaling pathway suppresses the immune escape of castration‑resistant prostate cancer to NK cells in hypoxia.

Castration‑resistant prostate cancer (CRPC) is difficult to treat in current clinical practice. Hypoxia is an important feature of the CRPC microenvironment and is closely associated with the progress of CRPC invasion. However, no research has been performed on the immune escape of CRPC from NK cells. The present study focused on this subject. Firstly, when the CRPC cell lines C4‑2 and CWR22Rv1 were induced by hypoxia, the expression of the UL16 binding protein (ULBP) ligand family of natural killer (NK) group 2D (NKG2D; ULBP‑1, ULBP‑2 and ULBP‑3) and MHC class I chain‑related proteins A and B

Recent advances in adoptive cell therapy for cancer immunotherapy.

Adoptive cell therapy (ACT), a key direction in tumor immunotherapy, has achieved remarkable progress in recent years. This paper systematically reviews the current status and future trends of ACT, covering lymphokine-activated killer cells (LAK), tumor-infiltrating lymphocytes (TIL), cytokine-induced killer cells (CIK), dendritic cells (DC), T cell receptor-modified T cells (TCR-T), chimeric antigen receptor T cells (CAR-T), natural killer (NK) cells, chimeric antigen receptor-modified NK cells (CAR-NK), and the emerging CAR-M. The paper focuses on emerging technological approaches, including

Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics.

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM's composition to restore its organization and function. Across diverse organ diseases, there are common denom

Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.

Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lympho

Challenges and breakthroughs: current landscape and future prospects of CAR-T cell therapy clinical trials for solid tumors.

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated significant efficacy in the treatment of hematological malignancies; however, its application in the solid tumor setting remains challenging. Given that solid tumors account for the vast majority of clinically diagnosed cancers, there is an urgent and significant clinical need to develop effective CAR-T therapy. This review focuses on the latest clinical trials of CAR-T therapy in major solid tumors, including glioma, colorectal, pancreatic, prostate, and lung cancers. It systematically evaluates the results of studies targeting

Fanconi anemia pathway as a prospective target for cancer intervention.

Fanconi anemia (FA) is a recessive genetic disorder caused by biallelic mutations in at least one of 22 FA genes. Beyond its pathological presentation of bone marrow failure and congenital abnormalities, FA is associated with chromosomal abnormality and genomic instability, and thus represents a genetic vulnerability for cancer predisposition. The cancer relevance of the FA pathway is further established with the pervasive occurrence of FA gene alterations in somatic cancers and observations of FA pathway activation-associated chemotherapy resistance. In this article we describe the role of th

Examining inpatient chemotherapy utilization among patients with cancer and impact on outcomes.

BackgroundWith the adoption of safer outpatient cancer care practices, much of cancer care has transitioned to outpatient settings, decreasing the need for inpatient systemic therapy (IST), which is associated with poorer end-of-life outcomes. We evaluated reasons for IST use, palliative care (PC) utilization, and outcomes among IST recipients to inform guidelines on appropriate IST use.Materials and methodsWe conducted a retrospective chart review of all IST admissions at an academic center from January 2016 to December 2017. Patients were stratified by solid tumor (ST) vs hematological malig

Характеристики и клинический курс пациентов с мелоидозом и раком.

У пациентов с активным раком больше шансов на развитие мелиоидоза, однако характеристики и клинический курс мелиоидоз у больных с раком не были подробно изучены. Профилактика триметоприма/сульфаметоксазола (TMP-SMX) предписывается для предотвращения мелоидоза у пациентов, получающих в некоторых юрисдикциях иммунную антираковую терапию, и рекомендуется в национальных австралийских руководящих принципах, хотя риски и выгоды этой стратегии определены не полностью. МЕТОДЫ: Исследование проводилось в Дальнем Северном Квинсленде (ФНК) в тропической Австралии. Характеристики и клинический курс пациен

The role of hypoxic microenvironment in autoimmune diseases.

The hypoxic microenvironment, characterized by significantly reduced oxygen levels within tissues, has emerged as a critical factor in the pathogenesis and progression of various autoimmune diseases (AIDs). Central to this process is the hypoxia-inducible factor-1 (HIF-1), which orchestrates a wide array of cellular responses under low oxygen conditions. This review delves into the multifaceted roles of the hypoxic microenvironment in modulating immune cell function, particularly highlighting its impact on immune activation, metabolic reprogramming, and angiogenesis. Specific focus is given to