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Antibody-Drug Conjugates for Cancer Therapy.

Antibody-drug conjugates (ADCs) are novel drugs that exploit the specificity of a monoclonal antibody (mAb) to reach target antigens expressed on cancer cells for the delivery of a potent cytotoxic payload. ADCs provide a unique opportunity to deliver drugs to tumor cells while minimizing toxicity to normal tissue, achieving wider therapeutic windows and enhanced pharmacokinetic/pharmacodynamic properties. To date, nine ADCs have been approved by the FDA and more than 80 ADCs are under clinical development worldwide. In this paper, we provide an overview of the biology and chemistry of each co

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… Inside the cytoplasm, the expression of the mitotic polo-like kinase 1 (PLK1) has been reported to confer T-DM1 resistance by completing mitosis despite the presence of an abnormal mitotic spindle and thus avoiding mitotic catastrophe by preventing cyclin-dependent kinase 1 (CDK1) activation. …

Nucleotide Metabolism in Health and Disease.

Nucleotide metabolism is a fundamental biochemical process, providing the building blocks for DNA and RNA synthesis while driving critical cellular functions like energy transfer, signal transduction, and coenzyme synthesis. The precise regulation of nucleotide de novo synthesis, salvage, and degradation pathways is imperative for maintaining genomic stability and tissue homeostasis. Aberrations in these networks are increasingly recognized as primary drivers in various pathologies; notably, cancer cells exploit metabolic-functional reprogramming to enable rapid proliferation and therapeutic r

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… In vitro exposure to these agents blocks cell cycle progression at mitosis and triggers the spindle checkpoint [ 319 ], prompting ROS accumulation. …

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

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… There is the presence of a typically large nucleus including hyperchromasia, dyskeratosis, and mitosis at the region of actinic keratocytic in the epidermal layer. … Interferons produce antiproliferative effects (by inhibiting mitosis and growth factor, by activation of pro-apoptotic genes, and by promoting antiangiogenic activity) on cancer cells and also support the immune system to fight against cancer-causing agents [ 204 ]. …

Abstracts of the 12th European Cytogenomics Conference 2019 : Salzburg, Austria. 6-9 July 2019

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The Role of Circulating MicroRNAs as Biomarkers and Therapeutic Targets in Venous Thromboembolism: A Systematic Review.

Introduction: Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cardiovascular disorder and a leading cause of vascular mortality. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate gene expression post-transcriptionally by binding to the target messenger RNAs (mRNAs), inducing mRNA degradation or translational repression. miRNA dysregulation likely contributes to VTE pathogenesis. This review comprehensively summarizes current evidence on miRNAs in VTE, offering a structured overview of the existing literature. Mate

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… NDUFA4 mitochondrial complex associated BECN1 | 604378 | beclin 1 | NEAT1 | 612769 | nuclear paraspeckle assembly transcript 1 long noncoding RNA (non-protein-coding RNA product) CASC2 | 608598 | cancer susceptibility 2 long noncoding RNA (non-protein-coding RNA product) | Nek2 | 604043 | never in mitosis …

RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.

In the last decades, colorectal cancer (CRC) has emerged as a global problem, representing approximately 10% of all malignant tumors and the second leading cause of cancer-related death. Colitis-associated cancer (CAC) arises from chronic unresolved inflammation and is typically characterised by poor prognosis. Among key cellular regulators, the small GTPase RHOA controls cytoskeleton dynamics in various cell types and, thereby, key biological processes. Although it has been linked to various diseases, the role of RHOA in cancer remains controversial. RHOA has been proposed as a biomarker in c

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… In physiological situations, RHOA activity is particularly important during the last steps of mitosis, anaphase, and telophase; GTP-RHOA localizes at the plasma membrane and cleavage furrow, and promotes the contractile ring, permitting cytokinesis and the division of the cytoplasm for the two daughter …

Витамин Д и здоровье: установление родственных отношений с помощью наблюдений и критериев Хилла в биологических рамках.

Витамин D связан с благоприятным воздействием более чем на 100 Здоровье, вызывающее значительный интерес к его внескелетным функциям. Однако, поскольку питательные вещества существенно отличаются от фармацевтических препаратов в биологии и механизмах действий, обычные выборочно контролируемые фармацевтические испытания (РСТ) часто не подходят для оценки эффективности питательных веществ. Вместо этого хорошо продуманные исследования наблюдений, в ходе которых оценивалась сыворотка 25-hydroxyvitamin Д [25Концентрации и их корреляция с биологически значимыми клиническими результатами свидетельств

Эпигенетика и метаболическая метаболическая дисфункция при многоразовом склерозе: обзор подходов к травяным лекарствам и текущих клинических испытаний.

Множественный склероз (MS) — сложная аутоиммунная болезнь, характеризующаяся воспалением, обезвоживанием и нейродегенерацией в центральной нервной системе (КНС). Хотя точные причины остаются неясными, недавние исследования подчеркивают важную роль эпигенетических изменений и митохондриальной дисфункции в начале и развитии болезни. Эпигенетические изменения, такие, как метилация ДНК, модификация гистона и регулирование микроРНК, влияют на генное выражение, не изменяя последовательности ДНК, что приводит к иммунной дисрегуляции и воспалению. Аналогичным образом, митохондриальная дисфункция, отме

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… Therefore, they can be passed on during cell meiosis and mitosis [ 67 ]. DNA methylation contributes to the diagnosis of MS, as it interferes with lymphocyte activity. DNA methylation is carried out in the brain tissues by enzymes known as DNA methyltransferases (DNMTs). …

A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy.

Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment of hematologic malignancies and solid tumors. Unlike conventional chemotherapeutic drug-based therapies, that are mainly associated with modest specificity and therapeutic benefit, the three key components that form an ADC (a monoclonal antibody bound to a cytotoxic drug via a chemical linker moiety) achieve remarkable improvement in terms of targeted killing of cancer cells and, while sparing healthy tissues, a reduction in systemic side effects caused by off-tum

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… As auristatin, by interfering with GTP hydrolysis on the β subunit, causes an excessive and sustained growth of microtubules, they lose the ability to shorten and separate sister chromatids in anaphase, causing cells to freeze in metaphase of mitosis ( Waight et al., 2016 ). 2.4 The development of ADC …

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.

Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue with poor outcome and little survivability of patients. The staging system has also been improved to better fit patient needs and to administer therapies in a more focused manner in consideration of pathology features. New and improved therapies have been developed; nevertheless, low efficacy and high

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… Age, Diagnostic Category, Tumor Grade, and Mitosis-Karyorrhexis Index are Independently Prognostic in Neuroblastoma: An INRG Project. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2020;38:1906–1918. doi: 10.1200/JCO.19.03285. 34. …

Biological and Clinical Aspects of Metastatic Spinal Tumors.

Spine metastases are a common life-threatening complication of advanced-stage malignancies and often result in poor prognosis. Symptomatic spine metastases develop in the course of about 10% of malignant neoplasms. Therefore, it is essential for contemporary medicine to understand metastatic processes in order to find appropriate, targeted therapeutic options. Thanks to continuous research, there appears more and more detailed knowledge about cancer and metastasis, but these transformations are extremely complicated, e.g., due to the complexity of reactions, the variety of places where they oc

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… The studies conducted on IGF-IR-disabled mice models have shown decreased mitosis and increased apoptosis of metastatic sites formed by breast cancer, multiple myeloma, neuroblastoma, and prostate cancer [ 94 ]. …

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention.

The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death pr

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… Recently, an HDAC 1 and -2-selective entinostat derivative, MPT0L184, was described to trigger premature mitosis with potential use to counteract cancer therapy resistance. …

PARP Inhibitors and Haematological Malignancies-Friend or Foe?

Since their introduction several years ago, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have become the standard of care for breast and gynaecological cancers with BRCA gene mutations. Given that PARPi act by exploiting defective DNA repair mechanisms within tumour cells, they should be ideally suited to combatting haematological malignancies where these pathways are notoriously defective, even though BRCA mutations are rare. To date, despite promising results in vitro, few clinical trials in humans for haematological malignancies have been performed, and additional investigation is

Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic.

Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung an

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… inflammation and tumor growth/spread, STAT3 contributes to tumor progression by upregulating cytokines, growth factors, and matrix metalloproteases. 44 , 47 – 50 In fact, STAT3 activation is common in tumor tissue, leading to increased growth and invasiveness via transcription of genes involved in mitosis …

Cancer evolution: mathematical models and computational inference.

Cancer is a somatic evolutionary process characterized by the accumulation of mutations, which contribute to tumor growth, clinical progression, immune escape, and drug resistance development. Evolutionary theory can be used to analyze the dynamics of tumor cell populations and to make inference about the evolutionary history of a tumor from molecular data. We review recent approaches to modeling the evolution of cancer, including population dynamics models of tumor initiation and progression, phylogenetic methods to model the evolutionary relationship between tumor subclones, and probabilisti

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… Although its exact cause is unclear, it is thought to be provoked by radiation exposure at a critical time point during cell cycle when chromosomes are condensed for mitosis. …

Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications.

Post-translational modifications (PTMs) play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality. PTMs involve the covalent attachment of distinct chemical groups, such as succinyl, crotonyl, and lactyl, at specific protein sites, which alter protein structure, function, stability, and activity, ultimately influencing biological processes. Recently, metabolically derived short-chain acylation modifications (with acyl groups containing fewer than six carbon atoms) have been progressively identified, such as butyrylation, succinylation, crotonylation

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

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… Among them, BRD4 is the most extensively studied, known for its ability to recruit positive transcription elongation factor b (P-TEFb), promote RNA polymerase II-driven elongation, and regulate gene expression even during mitosis [ 144 , 145 ]. …

Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then,

CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers.

CHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1's molecular functions, regulatory mechanisms, and effects in different pathological contexts. Specifically, the study objectives are to elucidate the biochemical pathways involving CHAC1, explore its regulatory network, and discuss its implications in disease progression and potential therapeutic strategies. As a γ-glutamyl cyclotrans

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

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… The FGFR 3- TACC 3 fusion protein is shown to be localized to mitotic spindle poles, according to research results, possesses inherent kinase activity, elicits abnormalities in mitosis and chromosome segregation, and instigates aneuploidy, ultimately leading to the development of tumorigenicity [ 70 …