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Chronic Liver Disease Associated Cholangiocarcinoma: Genomic Insights and Precision Therapeutic Strategies.

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy arising from the biliary epithelium, with an increasing incidence and poor prognosis worldwide. Recent advances in next-generation sequencing have revealed a variety of genomic alterations-such as FGFR2 fusions, IDH1 mutations, and ERBB2 amplification-that may serve as therapeutic targets. However, the influence of underlying etiologic factors, including chronic liver and biliary diseases, on the molecular landscape of CCA remains unclear. Objective: This review aimed to synthesize the current knowledge on the genomic an

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… Raf kinases: Function, regulation and role in human cancer. Biochim. Biophys. Acta (BBA) Mol. Cell Res. 2007;1773:1196–1212. doi: 10.1016/j.bbamcr.2007.05.001. 103. Bharti J., Gogu P., Pandey S.K., Verma A., Yadav J.P., Singh A.K., Kumar P., Dwivedi A.R., Pathak P. …

Small molecule inhibitors targeting the cancers.

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatme

CPUY201112, a novel synthetic small-molecule compound and inhibitor of heat shock protein Hsp90, induces p53-mediated apoptosis in MCF-7 cells.

Heat-shock protein 90 (Hsp90) is highly expressed in many tumor cells and is associated with the maintenance of malignant phenotypes. Targeting Hsp90 has had therapeutic success in both solid and hematological malignancies, which has inspired more studies to identify new Hsp90 inhibitors with improved clinical efficacy. Using a fragment-based approach and subsequent structural optimization guided by medicinal chemistry principles, we identified the novel compound CPUY201112 as a potent Hsp90 inhibitor. It binds to the ATP-binding pocket of Hsp90 with a kinetic dissociation (Kd) constant of 27

Molecular-targeted therapy toward precision medicine for gastrointestinal caner: Current progress and challenges.

Gastrointestinal (GI) cancer remains the deadliest cancer in the world. The current standard treatment for GI cancer focuses on 5-fluorouracil-based chemotherapeutic regimens and surgery, and molecular-targeted therapy is expected to be a more effective and less toxic therapeutic strategy for GI cancer. There is well-established evidence for the use of epidermal growth factor receptor-targeted and vascular endothelial growth factor-targeted antibodies, which should routinely be incorporated into treatment strategies for GI cancer. Other potential therapeutic targets involve the PI3K/AKT pathwa

From Bench to Bedside and Beyond: Therapeutic Scenario in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous group of clonal disorders characterized by abnormal proliferation of undifferentiated myeloid progenitors, impaired hematopoiesis, and variable response to therapy. To date, only about 30% of adult patients with AML become long-term survivors and relapse and/or disease refractoriness are the major cause of treatment failure. Thus, this is an urgent unmet clinical need and new drugs are envisaged in order to ameliorate disease survival outcomes. Here, we review the latest therapeutic approaches (investigational and approved agents) for AML treatme

Воздействие и механизмы N-3 и n-6 политетрафицированных жировых кислот в центральной нервной системе.

Мозг богат жирными кислотами (FAs) и полинунасыщенными жирными кислотами (PUFAs), такими, как докоза гексаэноиновая кислота (C22:6n-3, DHA) и арахидоническая кислота (C20:4n-6, ARA), причем первые в основном хранятся в виде фосфатидилэтилена, фосфатидила этаноламина (PE, диачила и плазма фосфолипид проформы) и фосфатидилсерин (PS), в то время как последние встречаются главным образом в фосфоглицеридах этаноламина (EPG) и составляют большинство фосфоглицеридов. По требованию организма ПФФА освобождаются от мембранных фосфолипидов (либо непосредственно, либо через их метаболиты, генерируемые сер

Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy.

The Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1 (SHP-1), a non-receptor protein tyrosine phosphatase, has been reported as a negative regulator of phosphorylated signal transducer and activator of transcription 3 (STAT3) and linked to tumor development. In this present review, we will discuss the importance and function of SHP-1/p-STAT3 signaling in nonmalignant conditions as well as malignancies, its cross-talk with other pathways, the current clinical development and the potential role of inhibitors of this pathway in anticancer therapy and clinical relevance of SHP

Combination Cancer Therapy and Reference Models for Assessing Drug Synergy in Glioblastoma.

Glioblastoma is currently an incurable disease despite the development of a wide variety of therapeutic approaches, from surgical methods to immunotherapy. In current clinical practice, treatment typically involves a combination of existing methods, often comprising three stages: tumor resection, radiotherapy, and chemotherapy. Modern research offers improved chemotherapy strategies, as well as combinations of chemotherapy with immunotherapy. However, the efficacy of these therapies is profoundly influenced by factors such as tumor and peritumoral heterogeneity, alongside complex molecular sig

Comprehensive review of targeted therapy for colorectal cancer.

Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world and was responsible for nearly 881,000 cancer-related deaths in 2018. Surgery and chemotherapy have long been the first choices for cancer patients. However, the prognosis of CRC has never been satisfying, especially for patients with metastatic lesions. Targeted therapy is a new optional approach that has successfully prolonged overall survival for CRC patients. Following successes with the anti-EGFR (epidermal growth factor receptor) agent cetuximab and the anti-angiogenesis agent bevacizumab, new agents

Translational Advances in Oncogene and Tumor-Suppressor Gene Research.

Cancer, characterized by the uncontrolled proliferation of cells, is one of the leading causes of death globally, with approximately one in five people developing the disease in their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology and progression, there is still a significant gap in knowledge about genetic aberrations and nuclear DNA damage. The study of two critical groups of genes-tumor suppressors, which inhibit proliferation and promote apoptosis, and oncogenes, which regulate proliferation and survival-can help to unde

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… Activated Ras then recruits Raf kinases to the cell membrane, specifically ARAF, BRAF, and CRAF (also known as RAF-1), which are serine/threonine kinase enzymes and isoforms of each other [ 72 , 73 ]. …

Medicinal chemistry perspectives on anticancer drug design based on clinical applications (2015-2025).

Cancer therapy has undergone a remarkable evolution over the past few decades, driven largely by innovations in medicinal chemistry. This review explores the pivotal role of medicinal chemistry in designing, optimizing, and classifying anticancer agents, from traditional cytotoxics to modern targeted therapies, immunotherapies, and radiotheranostics. The article categorizes FDA-approved anticancer drugs (2015-2025), evaluates their mechanisms of action, structural features, and structure-activity relationships (SAR), and highlights both success stories and challenges in clinical translation. A

Brown Tumour in Chronic Kidney Disease: Revisiting an Old Disease with a New Perspective.

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation

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… RAF kinases then phosphorylate and activate MEK (MAPK/ERK Kinase) proteins [ 65 ]. The activated MEK proteins, in turn, phosphorylate and activate MAPKs, including ERK1 (Extracellular Signal-Regulated Kinase 1) and ERK2 [ 66 ]. These activated MAPKs then translocate to the cell nucleus. …

Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer.

The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-kn

Trametinib in Patients With NF1-, GNAQ-, or GNA11-Mutant Tumors: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols S1 and S2.

PURPOSE: NCI-MATCH is a precision medicine trial using genomic testing to allocate patients with advanced malignancies to targeted treatment subprotocols. This report combines two subprotocols evaluating trametinib, a MEK1/2 inhibitor, in patients with Neurofibromatosis 1 (NF1[S1] or GNA11/Q [S2]) altered tumors. METHODS: Eligible patients had tumors with deleterious inactivating NF1 or GNA11/Q mutations by the customized Oncomine AmpliSeq panel. Prior MEK inhibitor treatment was excluded. Glioblastomas (GBMs) were permitted, including malignancies associated with germline NF1 mutations (S1 o

Hypertension and Prohypertensive Antineoplastic Therapies in Cancer Patients.

The development of a wide range of novel antineoplastic therapies has improved the prognosis for patients with a wide range of malignancies, which has increased the number of cancer survivors substantially. Despite the oncological benefit, cancer survivors are exposed to short- and long-term adverse cardiovascular toxicities associated with anticancer therapies. Systemic hypertension, the most common comorbidity among cancer patients, is a major contributor to the increased risk for developing these adverse cardiovascular events. Cancer and hypertension have common risk factors, have overlappi

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

Therapeutic Resistance in Acute Myeloid Leukemia: The Role of Non-Coding RNAs.

Acute myeloid leukemia (AML) is caused by malignant transformation of hematopoietic stem or progenitor cells and displays the most frequent acute leukemia in adults. Although some patients can be cured with high dose chemotherapy and allogeneic hematopoietic stem cell transplantation, the majority still succumbs to chemoresistant disease. Micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs) are non-coding RNA fragments and act as key players in the regulation of both physiologic and pathologic gene expression profiles. Aberrant expression of various non-coding RNAs proved to be of seminal im

Hypertension in Cardio-Oncology Clinic: an update on etiology, assessment, and management.

Hypertension is one of the most common comorbidity and the leading cause of cancer-related death in cancer patients. The prevalence of hypertension in cancer patients is much higher than that of the general population. In the older population of cancer patients, specific cancer treatments such as new tyrosine kinase inhibitors and Vascular endothelial growth factor inhibitor drugs give rise to hypertension in cancer patients; The aim of present study is to provide a detailed discussion etiologies of cancer treatment-induced hypertension and explore the most innovative diagnostic and management

Трансдифференциация новообразования плазменных клеток в острую миэлоидную лейкемию с моноциклическими характеристиками: сообщение о разном фенотипе с идентичным генотипом.

Myeloid malignatures после обработки опухолей плазменных клеток (PCN) встречается редко, но является серьезным осложнением, часто демонстрируя сложные кариотипы и мутации TP53. Нечасто сообщается о переходе на миелиоидную гадость с явной клональной связью. Здесь мы сообщаем об уникальном случае острой лейкемии миэлоида с моноцитической дифференциацией, которая разделяет клональные свойства с предшествующей плазменной клеточной миэломой с t (t)4;14) FGFR3:IGH. Это явление отличается от связанной с терапией миэлоидной неоплазмы, вызванной не связанным с ней клоном, и подчеркивает необходимость р

BRAF V600E liquid biopsy-based detection in precision oncology.

IntroductionThe BRAF V600E mutation is one of the most relevant genetic mutations in precision oncology. This variation is commonly found in several types of tumors, including melanoma, colorectal cancer, and thyroid cancer, to name a few. Liquid biopsy has emerged as a minimally-invasive screening option for this mutation.ContentThis review examines the molecular biology of the BRAF V600E mutation, its role in tumor progression, and its utility in the diagnosis, prognosis and treatment of specific types of tumors. In addition, the focus is also placed on liquid biopsy-based screening options