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Abscopal Effect in Radiation Therapy: The Immune Mechanisms and Clinical Advances.

The abscopal effect is a systemic antitumor response to localized radiotherapy (RT) that has emerged as a central focus in the era of immunotherapy. Clinical evidence demonstrates that local RT can induce regression of distant, nonirradiated metastases, including cases of complete remission. However, the effect remains unpredictable, with marked variation in clinical outcomes ranging from complete regression to paradoxical progression. The mechanistic basis for this heterogeneity and optimal strategies to enhance abscopal effects remain incompletely understood. This review synthesizes current

Utilization of redox modulating small molecules that selectively act as pro-oxidants in cancer cells to open a therapeutic window for improving cancer therapy.

There is a rapidly growing body of literature supporting the notion that differential oxidative metabolism in cancer versus normal cells represents a metabolic frailty that can be exploited to open a therapeutic window into cancer therapy. These cancer cell-specific metabolic frailties may be amenable to manipulation with non-toxic small molecule redox active compounds traditionally thought to be antioxidants. In this review we describe the potential mechanisms and clinical applicability in cancer therapy of four small molecule redox active agents: melatonin, vitamin E, selenium, and vitamin C

Coronary Artery Disease and Cancer: Treatment and Prognosis Regarding Gender Differences.

Cardiovascular disease and cancer remain the leading causes of hospitalization and mortality in high-income countries. Survival after myocardial infarction has improved but there is still a difference in clinical outcome, mortality, and developing heart failure to the disadvantage of women with myocardial infarction. Most major cardiology trials and registries have excluded patients with cancer. As a result, there is only very limited information on the effects of coronary artery disease in cancer patients. In particular, the outcomes in women with cancer and coronary artery disease and its ma

Cancer Immunotherapy Beyond Checkpoint Blockade: JACC: CardioOncology State-of-the-Art Review.

Avoidance of immune destruction is recognized as one of the hallmarks of cancer development. Although first predicted as a potential antitumor treatment modality more than 50 years ago, the widespread clinical use of cancer immunotherapies has only recently become a reality. Cancer immunotherapy works by reactivation of a stalled pre-existing immune response or by eliciting a de novo immune response, and its toolkit comprises antibodies, vaccines, cytokines, and cell-based therapies. The treatment paradigm in some malignancies has completely changed over the past 10 to 15 years. Massive effort

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

Orthogonal targeting of osteoclasts and myeloma cells for radionuclide stimulated dynamic therapy induces multidimensional cell death pathways.

Rationale: Multiple myeloma (MM) is a multifocal malignancy of bone marrow plasma cells, characterized by vicious cycles of remission and relapse that eventually culminate in death. The disease remains mostly incurable largely due to the complex interactions between the bone microenvironment (BME) and MM cells (MMC). In the "vicious cycle" of bone disease, abnormal activation of osteoclasts (OCs) by MMC causes severe osteolysis, promotes immune evasion, and stimulates the growth of MMC. Disrupting these cancer-stroma interactions would enhance treatment response. Methods: To disrupt this cycle

Modern therapeutic approaches in cholangiocarcinoma: A narrative review of key biomarkers and clinical trials.

Cholangiocarcinoma (CCA), the second most common hepatic malignancy after hepatocellular carcinoma, presents a significant clinical challenge. This epithelial cell malignancy occurs in various anatomical subtypes, including intrahepatic, perihilar, and distal, each associated with unique genetic aberrations, clinical presentations, and treatment options. Early diagnosis is challenging, leading to poor survival rates, especially in advanced cases. Precision medicine offers hope for improved management of CCA by tailoring treatments based on molecular profiling. In recent years, the investigatio

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Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.

Endoplasmic reticulum (ER) stress is a key cellular mechanism that is important in the development of many diseases, including cancer. Since the discovery of the unfolded protein response (UPR), research has greatly improved our understanding of how ER stress affects cellular functions, especially protein folding and adaptation to stress. The UPR consists of three main branches: IRE1, ATF6, and PERK, each of which is crucial for regulating stress responses, protein homeostasis, and apoptosis. These pathways normally help cells handle stress effectively; however, excessive or prolonged activati

Research Progress of NK Cells in Glioblastoma Treatment.

NK cells are a type of antitumor immune cell with promising clinical application, following T cells. The activity of NK cells is primarily regulated by their surface receptors and immune microenvironment. In gliomas, the tumor microenvironment exerts a strong immunosuppressive effect, which significantly reduces the clinical efficacy of NK cell immunotherapy. Therefore, this review aims to discuss the latest research on the role of NK cells in glioma immunotherapy, focusing on aspects such as NK cell development, function, and localization. It summarizes information on the compounds, monoclona

CAR-T cells in the treatment of multiple myeloma: an encouraging cell therapy.

Multiple myeloma (MM) is a malignant disease of plasma cells that accounts for approximately 10% of all hematological malignancies and is characterized by a clonal proliferation of malignant plasma cells in the bone marrow. Numerous therapeutic strategies, including proteasome inhibitors, immunomodulators, monoclonal antibodies against CD38 and autologous stem cell transplantation, have prolonged the median survival of MM patients. Nevertheless, almost all MM patients suffer disease relapses due to drug resistance and eventually die from MM or MM-related complications. Chimeric antigen recepto

Olive Leaf Extract (OLE) Anti-Tumor Activities Against Hematologic Tumors: Potential Therapeutic Implications for Pediatric Patients with B-Acute Lymphoblastic Leukemia.

Background/Objectives: Several studies reported that olive leaf extract (OLE) may exert potent anti-cancer activities against human solid and hematological tumors. Such effects are mostly related to the polyphenol oleuropein and its derivatives, which are highly concentrated in OLE. Here, we investigated the anti-tumor effects of OLE in vitro against human acute leukemia and lymphoma cells. Methods: Cell proliferation and apoptosis have been evaluated by flow cytometry (using CFSE and Annexin-V/7AAD, respectively) in the presence or absence of OLE at different concentrations and in combination

Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.

Zinc metabolism at the cellular level is critical for many biological processes in the body. A key observation is the disruption of cellular homeostasis, often coinciding with disease progression. As an essential factor in maintaining cellular equilibrium, cellular zinc has been increasingly spotlighted in the context of disease development. Extensive research suggests zinc's involvement in promoting malignancy and invasion in cancer cells, despite its low tissue concentration. This has led to a growing body of literature investigating zinc's cellular metabolism, particularly the functions of

Therapeutic potential of Fingolimod in triple negative breast cancer preclinical models.

Surgery followed by a chemotherapy agent is the first-line treatment for breast cancer patients. Nevertheless, new targets are required for women with triple-negative breast cancer (TNBC) in order to improve the treatment of this aggressive cancer subtype. Multiple pro-inflammatory molecules including lipid-based substances such as sphingosine-1-phosphate (S1P) promote cancer progression. In this preclinical study, we aim to investigate the efficacy of Fingolimod, an inhibitor of S1P / S1P receptors axis, already approved as an immunomodulator in multiple sclerosis. The impact of Fingolimod wa

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… FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells. PLoS One. 2012;7 doi: 10.1371/journal.pone.0032380. 59. Pereira F.V., Arruda D.C., Figueiredo C.R., Massaoka M.H., Matsuo A.L., Bueno V. …

The Past, Present, and Future of Clinically Applied Chimeric Antigen Receptor-T-Cell Therapy.

Immunotherapy represents the fourth pillar of cancer therapy after surgery, chemotherapy, and radiation. Chimeric antigen receptor (CAR)-T-cell therapy is an artificial immune cell therapy applied in clinical practice and is currently indicated for hematological malignancies, with cluster of differentiation 19 (CD19) as its target molecule. In this review, we discuss the past, present, and future of CAR-T-cell therapy. First, we summarize the various clinical trials that were conducted before the clinical application of CD19-targeted CAR-T-cell therapies began. Second, we discuss the accumulat

A Tailored Approach for Appendicular Impending and Pathologic Fractures in Solid Cancer Metastases.

Advances in medical and surgical treatment have played a major role in increasing the survival rates of cancer patients with metastatic bone disease. The clinical course of patients with bone metastases is often impaired by bone complications, such as bone fractures, which have a substantial negative impact on clinical outcomes. To optimize clinical results and prevent a detrimental impact on patients' health, a tailored approach should be defined for any given patient. The optimal management of impending or pathologic fractures is unknown and relies on a multidisciplinary approach to tailor c

Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks.

Cancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host's immune capacity to eliminate tumors. Although some success has been seen in this field, toxicity and weak immune induction remain challenges. Liposomal nanosystems, previously used as targeting agents, are increasingly functioning as immunotherapeutic vehicles, with potential for delivery of contents, immune induction, and synergistic drug packaging. These systems are tailorable, multifunctional,

Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in genome-editing technologies and promising clinical trial data, significant challenges remain, including graft-

Cellular and Molecular Mechanisms Associating Obesity to Bone Loss.

Obesity is an alarming disease that favors the upset of other illnesses and enhances mortality. It is spreading fast worldwide may affect more than 1 billion people by 2030. The imbalance between excessive food ingestion and less energy expenditure leads to pathological adipose tissue expansion, characterized by increased production of proinflammatory mediators with harmful interferences in the whole organism. Bone tissue is one of those target tissues in obesity. Bone is a mineralized connective tissue that is constantly renewed to maintain its mechanical properties. Osteoblasts are responsib

An Overview of Advances in Rare Cancer Diagnosis and Treatment.

Cancer stands as the leading global cause of mortality, with rare cancer comprising 230 distinct subtypes characterized by infrequent incidence. Despite the inherent challenges in addressing the diagnosis and treatment of rare cancers due to their low occurrence rates, several biomedical breakthroughs have led to significant advancement in both areas. This review provides a comprehensive overview of state-of-the-art diagnostic techniques that encompass new-generation sequencing and multi-omics, coupled with the integration of artificial intelligence and machine learning, that have revolutioniz