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Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brai

CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.

CRISPR-Cas9 has progressed from an experimental tool to a therapeutic modality, marked by the first regulatory approvals of an ex vivo-edited autologous CD34+ hematopoietic stem cell product that induces fetal hemoglobin (CASGEVY/exa-cel). In this narrative review, we synthesize modality-specific molecular diagnostic strategies used across early CRISPR clinical translation. In parallel, early clinical experience has begun to demonstrate the feasibility of in vivo editing, including subretinal delivery for CEP290-associated inherited retinal degeneration (EDIT-101 programme) and hepatocyte-targ

MYC inhibitors in multiple myeloma.

The importance of MYC function in cancer was discovered in the late 1970s when the sequence of the avian retrovirus that causes myelocytic leukemia was identified. Since then, over 40 years of unceasing research have highlighted the significance of this protein in malignant transformation, especially in hematologic diseases. Indeed, some of the earliest connections among the higher expression of proto-oncogenes (such as MYC), genetic rearrangements and their relation to cancer development were made in Burkitt lymphoma, chronic myeloid leukemia and mouse plasmacytomas. Multiple myeloma (MM), in

The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance.

Bone metastases represent frequent and severe complications in various cancers, notably impacting prognosis and quality of life. This review article delves into the genetic and epigenetic mechanisms underpinning drug resistance in bone metastases, a key challenge in effective cancer treatment. The development of drug resistance in cancer can manifest as either intrinsic or acquired, with genetic heterogeneity playing a pivotal role. Intrinsic resistance is often due to pre-existing mutations, while acquired resistance evolves through genetic and epigenetic alterations during treatment. These a

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, includ

MM-129 as a Novel Inhibitor Targeting PI3K/AKT/mTOR and PD-L1 in Colorectal Cancer.

Background and aimsThe purpose of the present study was to examine the pharmacodynamics features of MM-129 (1,2,4-triazine derivative) as a novel promising drug candidate against colon cancer.MethodsMM-129 was assessed for antitumor activity through an in vivo study on Cby.Cg-Foxn1nu/cmdb mice. The mechanistic studies investigated cellular affinity of a new 1,2,4-triazine derivative by measuring levels of intracellular/extracellular signal molecules participating in tumorigenesis.ResultsThe results revealed that MM-129 significantly reduced tumor growth in mice challenged with DLD-1 and HT-29

Biomarker Jeopardy.

In the popular Biomarker Jeopardy session, Sandra E. Kurtin, PhD, ANP-C, AOCN®, Alyssa Henglefelt, PharmD, BCOP, and Haleigh Mistry, MS, PA-C, paired biomarkers with tumor types for which their expression is most commonly used to determine targeted therapy, identified key assays used to measure common biomarkers, and discussed guidelines for biomarker testing.

Basket Trials for Intractable Cancer.

Currently, genomic characterization has become standard of care for tumor types such as non-small cell lung cancer, breast cancer, melanoma, and colorectal cancer. A deep understanding of genomic alterations in different tumor types would help identify potentially actionable genomic changes which occur across a wide variety of tumor types. A basket trial is a new type of clinical trial for which eligibility is based on the presence of a specific genomic alteration, irrespective of histology. Basket trials are phase II screening trials for the off-label use of a targeted drug in patients with t

Repurposing nirogacestat, a gamma secretase enzyme inhibitor in desmoid tumors.

The gamma secretase (GS) enzyme controls cell-cell adhesion, neural stem cell proliferation, neo-angiogenesis, spinal maturation, and metabolism of amyloid precursor proteins (APP). Pathological production of abnormal amyloid-beta isoforms and senile plaques serves as the basis for pathogenesis of Alzheimer's disease (AD). GS enzyme inhibitors such as semagacestat and avagacestat were explored in AD but the studies were paused because of adverse events attributed to their influence on the Notch pathway.Crosstalk between Notch and Wnt signaling pathways created a potential role for GS inhibitor

Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.

Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with elevated tumor-initiating potential. Upon differentiation, they replenish the bulk of the tumor cell population. Enhanced tumor-forming capacity, resistance to antitumor drugs, and metastasis-forming potential are the hallmark traits of CSCs. Given these properties, it is not surprising that CSCs have become a therapeutic target of prime interest in drug discovery. In fact, over the last few years, an enormous number of articles describing compounds endowed with anti-CSC activities have been published. In the meanwhile,

FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy.

BackgroundFifty percent of patients with muscle-invasive bladder cancer (MI-BC) die from their disease and current chemotherapy treatment only marginally increases survival. Novel therapies targeting receptor tyrosine kinases or activated oncogenes may improve outcome. Hence, it is necessary to stratify patients based on mutations in relevant oncogenes. Patients with non-muscle-invasive bladder cancer (NMI-BC) have excellent survival, however two-thirds develop recurrences. Tumor specific mutations can be used to detect recurrences in urine assays, presenting a more patient-friendly diagnostic

Combination of bortezomib plus ruxolitinib in steroid-refractory chronic graft-versus-host disease.

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Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy.

Despite the great advancements made in cancer treatment, there are still many unsatisfied aspects, such as the wide palette of side effects and the drug resistance. There is an obvious increasing scientific attention towards nature and what it can offer the human race. Natural products can be used to treat many diseases, of which some plant products are currently used to treat cancer. Plants produce secondary metabolites for their signaling mechanisms and natural defense. A variety of plant-derived products have shown promising anticancer properties in vitro and in vivo. Rather than recreating

Anti-Inflammatory Drugs as Anticancer Agents.

Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasin

Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches.

Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, tr

Совпадение в полном тексте источника
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Effects and mechanisms of Eps8 on the biological behaviour of malignant tumours (Review).

Epidermal growth factor receptor pathway substrate 8 (Eps8) was initially identified as the substrate for the kinase activity of EGFR, improving the responsiveness of EGF, which is involved in cell mitosis, differentiation and other physiological functions. Numerous studies over the last decade have demonstrated that Eps8 is overexpressed in most ubiquitous malignant tumours and subsequently binds with its receptor to activate multiple signalling pathways. Eps8 not only participates in the regulation of malignant phenotypes, such as tumour proliferation, invasion, metastasis and drug resistanc

Update on current pancreatic treatments: from molecular pathways to treatment.

Pancreatic cancer is still diagnosed at a late stage although we have novel diagnostic tools. Pancreatic cancer chemotherapy treatment resistance is observed and therefore novel treatments are in need. Anti-cancer stem cell therapy, combination of chemotherapy and/or radiotherapy with immunotherapy, proteins/enzymes and gene therapy are currently under evaluation. Targeted treatment with tyrosine kinase inhibitors is also administered and novel inhibitors are also under evaluation. In the current review we present recent data from our search within the year 2018.

Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics.

Since November 2019 the SARS-CoV-2 pandemic has caused nearly 200 million infection and more than 4 million deaths globally (Updated information from the World Health Organization, as on 2nd Aug 2021). Within only one year into the pandemic, several vaccines were designed and reached approval for the immunization of the world population. The remarkable protective effects of the manufactured vaccines are demonstrated in countries with high vaccination rates, such as Israel and UK. However, limited production capacities, poor distribution infrastructures and political hesitations still hamper th

Поврежденное когнитивное и поведенческое функционирование в детском возрасте и экономические результаты взрослой жизни.

Метформин был назван следующим: one :: из наиболее важных медицинских агентов первой линии в управлении типом 2 Болит диабет. Поскольку метформин является главным образом антигипергликемическим агентом, он также оказывает огромное влияние на различные системы и процессы. Он действует главным образом путем активации AMPK (Adenosine Monophosphate-Activated Protein Kinase) в клетках и сокращения выхода глюкозы из печени. Кроме того, она сокращает производство современных продуктов гликации и реактивных видов кислорода в эндотелии, помимо регулирования глюкозы и липидного метаболизма в кардиомиоки

Adjuvant Properties of Caffeic Acid in Cancer Treatment.

Caffeic acid (CA) is a polyphenol belonging to the phenylpropanoid family, commonly found in plants and vegetables. It was first identified by Hlasiwetz in 1867 as a breakdown product of caffetannic acid. CA is biosynthesized from the amino acids tyrosine or phenylalanine through specific enzyme-catalyzed reactions. Extensive research since its discovery has revealed various health benefits associated with CA, including its antioxidant, anti-inflammatory, and anticancer properties. These effects are attributed to its ability to modulate several pathways, such as inhibiting NFkB, STAT3, and ERK