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Expression and clinical significance of programmed death ligand-1 evaluated by 22C3 antibody in pleural effusion metastatic non-small-cell lung cancer.

ObjectiveProgrammed death ligand-1 (PD-L1) is involved in tumor immune escape and is an important target molecule for the immunotherapy of non-small-cell lung cancer (NSCLC). The expression of PD-L1 affects NSCLC invasion, metastasis, and patient survival. This study aims to explore the levels of PD-L1, as identified by the 22C3 antibody, in the malignant pleural effusion of patients suffering from advanced NSCLC, and to determine its clinical implications.Material and methodsA two-step immunohistochemical EnVision assay was used to evaluate the expression of PD-L1 by the 22C3 antibody in 149

The Precision Revolution in Hematologic Malignancies: A Decade of Transformative Immunotherapies and Targeted Agents.

This review describes the dramatic transformation that has occurred in the last ten years in the therapeutic landscape for hematologic malignancies, such as leukemias, lymphomas, myelomas, and myelodysplastic syndromes. Treatment paradigms have quickly changed from depending solely on cytotoxic chemotherapy to embracing precision medicine, driven by a previously unprecedented understanding of disease biology and precise molecular changes. The development of powerful immunotherapies (such as CAR T-cell therapy and bispecific antibodies) and innovative targeted agents (like BTK inhibitors, BCL-2

Pharmacomicrobiomics in Anticancer Therapies: Why the Gut Microbiota Should Be Pointed Out.

Anticancer treatments have shown a variable therapeutic outcome that may be partly attributable to the activity of the gut microbiota on the pathology and/or therapies. In recent years, microbiota-drug interactions have been extensively investigated, but most of the underlying molecular mechanisms still remain unclear. In this review, we discuss the relationship between the gut microbiota and some of the most commonly used drugs in oncological diseases. Different strategies for manipulating the gut microbiota layout (i.e., prebiotics, probiotics, antibiotics, and fecal microbiota transplantati

High-Dose Vitamin C for Cancer Therapy.

In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C could be effectively utilized in the management of various tumor types. Studies have shown that the pharmacological action of Vit-C can attack various processes that cancerous cells use for their growth and development. Here, we discuss the anti-cancer functions of Vit-C, but also the potenti

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… One study revealed that a daily intraperitoneal administration of high-dose Vit-C (4 g/kg) inhibited the growth of neuroblastoma and ovarian cancer in a xenograft model, with increased checkpoint kinase 2 (CHK2), as well as histone 2AX (H2AX) function in malignancies resulting in DNA damage, which may …

In vitro models of breast cancer bone metastasis: analyzing drug resistance through the lens of the microenvironment.

Even though breast cancers usually have a good outcome compared to other tumors, the cancer can progress and create metastases in different parts of the organism, the bone being a predilection locus. These metastases are usually the cause of death, as they are mostly resistant to treatments. This resistance can be caused by intrinsic properties of the tumor, such as its heterogeneity, but it can also be due to the protective role of the microenvironment. By activating signaling pathways protecting cancer cells when exposed to chemotherapy, contributing to their ability to reach dormancy, or ev

Antibody-Antineoplastic Conjugates in Gynecological Malignancies: Current Status and Future Perspectives.

In the last decade, antibody-drug conjugates (ADCs), normally formed by a humanized antibody and a small drug via a chemical cleavable or non-cleavable linker, have emerged as a potential treatment strategy in cancer disease. They allow to get a selective delivery of the chemotherapeutic agents at the tumor level, and, consequently, to improve the antitumor efficacy and, especially to decrease chemotherapy-related toxicity. Currently, nine antibody-drug conjugate-based formulations have been already approved and more than 80 are under clinical trials for the treatment of several tumors, especi

Existing and emerging strategies for fertility preservation in female patients with leukemia.

Leukemia, the most common malignancy in childhood, affects individuals from prepubertal girl to women of reproductive age. It originates from immature hematopoietic cells in the bone marrow and disseminates systemically via the blood and lymphatic circulations. Although survival rates have improved substantially, standard treatments, including intensive chemotherapy and hematopoietic stem cell transplantation, often combined with total body irradiation, are highly gonadotoxic. Consequently, a significant proportion of survivors experience long-term endocrine dysfunction and infertility, with f

Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword.

Multiple myeloma (MM) is a hematological malignancy defined by the abnormal proliferation and accumulation of plasma cells (PC) within the bone marrow (BM). While multiple myeloma impacts the bone, it is not classified as a primary bone cancer. The bone marrow microenvironment significantly influences the progression of myeloma and its treatment response. Mesenchymal stromal cells (MSCs) in this environment engage with myeloma cells and other bone marrow components via direct contact and the secretion of soluble factors. This review examines the established roles of MSCs in multiple facets of

Hijacking the helpers: platelet and neutrophil trafficking in AML and therapeutic exploitation.

Acute myeloid leukemia (AML) remains one of the most aggressive and treatment-resistant hematologic malignancies, driven by clonal expansion of immature myeloid blasts in the bone marrow and peripheral blood. Current therapies-chemotherapy and targeted agents-are limited by poor marrow penetration, systemic toxicity, and rapid development of resistant clones, leaving long-term survival rates low. Clinicians face the persistent challenge of delivering effective therapy while minimizing harm. Platelets and neutrophils-beyond their classical roles in hemostasis and innate immunity-actively suppor

Cancer Therapy-Induced Encephalitis.

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients' quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy-particularly immune checkpoint inhibitors-has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as im

Plants as a Source of Anticancer Agents: From Bench to Bedside.

Cancer is the second leading cause of death after cardiovascular diseases. Conventional anticancer therapies are associated with lack of selectivity and serious side effects. Cancer hallmarks are biological capabilities acquired by cancer cells during neoplastic transformation. Targeting multiple cancer hallmarks is a promising strategy to treat cancer. The diversity in chemical structure and the relatively low toxicity make plant-derived natural products a promising source for the development of new and more effective anticancer therapies that have the capacity to target multiple hallmarks in

Cellular based treatment modalities for unresectable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is unfortunately associated with an overall poor prognosis and high mortality. Early and intermediate stages of HCC allow for treatment with surgical resection, ablation and even liver transplantation, however disease progression warrants conventional systemic therapy. For years treatment options were limited to molecular-targeting medications, of which sorafenib remains the standard of care. The recent development and success of immune checkpoint inhibitors has proven to be a breakthrough in the treatment of

Targeting FGFR for cancer therapy.

The FGFR signaling pathway is integral to cellular activities, including proliferation, differentiation, and survival. Dysregulation of this pathway is implicated in numerous human cancers, positioning FGFR as a prominent therapeutic target. Here, we conduct a comprehensive review of the function, signaling pathways and abnormal alterations of FGFR, as well as its role in tumorigenesis and development. Additionally, we provide an in-depth analysis of pivotal phase 2 and 3 clinical trials evaluating the performance and safety of FGFR inhibitors in oncology, thereby shedding light on the current

CAR-T therapy for neuroendocrine neoplasms: a review of molecular targets and clinical translation.

Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies. In metastatic and progressive forms, standard therapies are often ineffective. CAR-T therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is considered a promising approach for NEN treatment, despite significant barriers inherent to solid tumors. This review aims to comprehensively analyze and systematize current scientific data on the development of CAR-T therapy for NENs of various origins. It focuses on relevant molecular targets, preclinical findings demonstrating the efficacy and s

Immunotherapies for pediatric cancer: current landscape and future perspectives.

The advent of immunotherapy has revolutionized how we manage and treat cancer. While the majority of immunotherapy-related studies performed to date have focused on adult malignancies, a handful of these therapies have also recently found success within the pediatric space. In this review, we examine the immunotherapeutic agents that have achieved the approval of the US Food and Drug Administration for treating childhood cancers, highlighting their development, mechanisms of action, and the lessons learned from the seminal clinical trials that ultimately led to their approval. We also shine a

Моделирование и нацеливание враждебной физико-химической ниши в метастазе костей: от экспериментальных платформ до нишевой терапии.

Метастаз рака до костей формируется не только из-за перекрестка опухолей, но и из-за враждебной физико-химической ниши, которая способствует стойкости к болезням и терапевтической недостаточности. Гипоксия, кислотность, минерализированная матричная архитектура, изменённая механика, интерстициальное давление, дисфункция перфузии и ограниченный перенос наркотиков влияют на метастатическое семя, общность, реактивацию, реконструкцию, боль и реакцию на лечение. Обычные two- размерные культуры и многие упрощенные three- размерные системы воспроизводят только отдельные особенности этой среды, часто п

Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy.

The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling

Update Breast Cancer 2019 Part 5 - Diagnostic and Therapeutic Challenges of New, Personalised Therapies in Patients with Advanced Breast Cancer.

Significant advancements have been made in recent years in advanced breast cancer and nearly all of them have been in the field of targeted therapy. Pertuzumab and trastuzumab-emtansine (T-DM1) have been able to be introduced in HER2-positive breast cancer. Now other anti-HER2 therapies are being developed (e.g. margetuximab, DS-8201a, pyrotinib) which can overcome other resistance mechanisms in the HER2 signalling pathway. In the field of hormone-receptor-positive breast cancer, an mTOR inhibitor and CDK4/6 inhibitors were introduced in the past. Now the introduction of the first PI3K inhibit

RNA modifications in cancer.

RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), are implicated in various cellular processes. These modifications are regulated by proteins that write, erase, and read RNA and modulate RNA stability, splicing, translation, and degradation. Recent studies have highlighted their roles in metabolic reprogramming, signaling pathways, and cell cycle control, which are essential for tumor proliferation and survival. Despite these scientific advances, the precise

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