The c-Jun N-terminal protein kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family. JNK1, JNK2, and JNK3 are three isoforms encoded by distinct genes. JNK signaling controls a variety of biological functions, such as cell proliferation, survival, apoptosis, and differentiation. Additionally, it controls the death and survival of cancer cells. Many studies show that JNK-driven tumorigenesis plays a major role in various cancers. Because JNKs are potential targets for cancer therapy since they are activated aberrantly in many cancers, the development of efficient and specific JNK inhibitors is the current focus in cancer therapeutics. This review provides insights into the development of new JNK inhibitors for the treatment of cancer and enhances understanding of JNK's involvement in cancer progression.

Nucleolar-spindle-associated protein 1 (NUSAP1) participates in the assembly of microtubules and the mitotic spindle. Mitotic spindles are microtubule-based structures that segregate chromosomes during mitosis. Its overexpression and knockdown caused alterations in gene expression programs linked to tumor progression. It was also identified as one of the potential hub genes in various cancers, including the mediation of hepatocellular carcinoma. The present research addresses the NUSAP1 protein structure refinement and its targeting by the lead molecules identified using various computational approaches. The initial structure of NUSAP1 from the Alpha fold database is evaluated using the Ramachandran plot and subjected to multiple energy minimization steps through the YASARA program. The best-optimized structure of NUSAP1 is obtained and subjected to binding site analysis and virtual screening studies using I-TASSER and Mcule webservers, respectively. From the binding site analysis, His293 was considered the ligand binding site for docking ligands by AutoDock Vina. Selected ligands from the Mcule chemical library were chosen through various filters, and 50 hits were identified for further studies. Among the 50 hits, 27 were identified as non-toxic molecules using a toxicity checker. Further, based on the RO5 violation check, 18 hits exhibited no RO5 violations. Further, for all 18 hits, LigPlot analysis was performed, and 11 hits exhibited hydrogen and hydrophobic interactions with the NUSAP1 protein. Among 11, three hits showed promising hydrogen and hydrophobic interactions near the potential binding site His293. For the promising three hits with Mcule IDs 9300000909-0-6, 9753624331-0-3, and 1764527053-0-4, ADMET properties were predicted using the PreADMET server. The comparative studies of drug-likeness properties found that all three hits do not violate Lipinski's rule of 5. The comparative studies of ADME properties of three hits found that the 9753624331-0-3 compound exhibits non-inhibiting properties in liver enzymes and p-glycoprotein inhibition. Furthermore, 9753624331-0-3 is computed as the lowest solvation-free energy of -18.1300000 and found to be non-mutagenic, negative for all toxicity studies, including the Ames test, fishes, rats, mice, and daphnia. Based on the drug-likeness, ADME, and toxicity predictions, the 9753624331-0-3 presented favorable properties and hence may be considered the potential lead targeting the NUSAP1 protein.

Immunogenic cell death (ICD) is a regulated form of cell death that elicits an adaptive immune response, recognized as a promising strategy in cancer immunotherapy. Its therapeutic efficacy, however, can be influenced by tumor-intrinsic factors, particularly in heterogeneous diseases like breast cancer (BC). This study investigated the ICD-related gene expression signature in BC using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohorts. Analysis revealed significantly elevated expression of HSP90AA1, CXCR3, MYD88, FOXP3, PDIA3, XBP1, and IFNB1, and reduced expression of P2RX7 in BC tissues compared with normal tissues. Furthermore, the expression of these genes varied significantly across distinct BC subtypes, patient ages, and tumor stages. Concurrently, an investigation into the UPR pathway, known to intersect with ICD, highlighted Binding immunoglobulin Protein (BiP/GRP78/HSPA5) as a molecule of interest. To explore potential modulators of this pathway, in silico docking studies were performed, which predicted favorable binding interactions of quercetin and taxifolin with BiP. These findings suggest that characterizing the expression patterns of these ICD-related genes and UPR components could inform the development of personalized immunotherapeutic strategies for BC, tailored to specific tumor subtypes, stages, and patient demographics. Further exploration of BiP's role and its potential for therapeutic manipulation may offer novel avenues to enhance anti-tumor immunity.

Key molecular pathways involved in colorectal cancer (CRC) progression include the activation of the heat shock protein 90 (HSP90) pathway, PI3K/AKT, TP53, and mismatch repair (MMR) pathways. In the current study, we identified that FKBP4 is overexpressed at the transcript and translational levels in CRC patient samples, suggesting it may be a predictive biomarker for diagnosis. Our STRING network data analysis identified a strong association (string score: 0.999) between FKBP4 and HSP90. HSP90 is involved in stability, transportation, and protein folding. TCGA CRC patient samples data revealed a strong positive correlation between FKBP4 and HSP90. Furthermore, molecular docking, dynamics simulations, and hydrogen bond analysis confirmed a strong interaction between FKBP4 and HSP90, suggesting its importance in CRC cell survival and progression. These findings highlight that disrupting the FKBP4-HSP90 complex could be a promising therapeutic approach for CRC.

Colon cancer (CC) is the 3rd most prevalent cancer globally, following breast and lung cancer, with the second-highest mortality rate. Multiple risk factors contribute to CC, and metastasis is the primary cause of increased mortality among CC patients. Natural compounds have been investigated for their ability to concurrently influence various carcinogenic mechanisms by interfering with the expression or activity of their signaling targets. This review focuses on natural flavonoids such as quercetin, taxifolin, and rutin. We discuss how these bioactive compounds potentially mitigate metastasis and associated signaling pathways in colon cancer.

The immune microenvironment of the three most common gynaecological malignancies-tubo-ovarian cancer, endometrial cancer and cervical cancer-has not been systematically studied, limiting clinical application.

Tropomyosin 3 (TPM3), one of the four tropomyosin genes, is predominantly expressed in eukaryotic cells. As a crucial regulatory protein, TPM3 associates with actin within thin myofilaments, thereby playing an essential role in the regulation of muscle contraction. Beyond its fundamental function in muscle physiology, TPM3 is implicated in oncogenesis.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, with often a high Ki-67 proliferation index. Prognosis is associated with lymphoma stage, lactate dehydrogenase level, and metabolic tumor volume. Thus, intuitively, time from symptom onset to diagnosis would be assumed to be essential for treatment outcome, but existing literature is conflicting.

In esophageal squamous cell carcinoma, three-field lymph node dissection (3FLND) is not commonly performed after neoadjuvant chemoradiotherapy (nCRT) due to the high morbidity associated with the procedure and the poor long-term survival of patients with cervical/supraclavicular lymph node metastasis. This study aims to evaluate the long-term survival outcomes of patients who underwent 3FLND combined with nCRT.

Follicular cell-derived thyroid carcinomas (FCTC) are common, with stable mortality rates but significant recurrence risks. Extrathyroidal extension (ETE) affects recurrence risk and staging. The 8th edition of the AJCC/TNM classification excludes microscopic ETE from upstaging but considers gross ETE a significant factor in older patients.

The coronavirus disease 2019 (COVID-19) pandemic disrupted cancer care, resulting in significant diagnostic delays.

An arachnoid cyst of the third ventricle of the brain is a rare condition. The paucity of information regarding these cysts makes their accurate diagnosis and optimal treatment a subject of discussion. Despite several techniques that exist for its treatment, endoscopic fenestration of the cyst should be considered the first line of management in symptomatic patients, as it is associated with fewer complications and a better outcome.

Central nervous system (CNS) embryonal tumors are a subset of aggressive pediatric brain tumors, more frequently seen in infants and young children. They share an aggressive imaging appearance with frequent disseminated disease and guarded prognosis; however, patient age, tumor location, and imaging characteristics such as enhancement pattern and peritumoral edema can help with differential diagnosis. In this article, we have reviewed medulloblastoma, atypical teratoid rhabdoid tumor, embryonal tumor with multilayered rosettes as well as newly recognized CNS neuroblastoma, FOXR2-activated and CNS tumor with BCOR internal tandem duplication.

The 2021 WHO Brain Tumor classification update grouped ependymal tumors into 3 anatomic locations-supratentorial, posterior fossa, and spinal. Supratentorial ependymomas now include ZFTA-fusion tumors which are often cystic, hemorrhagic, and show marked edema and YAP1-fusion tumors which demonstrate garlanded peripheral solid enhancement and diffusion-restriction. Posterior fossa ependymomas are now grouped by methylation profile into category A-typical posterior fossa ependymoma and category B which present in older children with smaller lesions with a better prognosis. Spinal ependymoma is relatively unchanged by molecular characterization apart from the new MYCN-altered tumor which has poor prognosis and is often advanced/disseminated at presentation.

Glioneuronal tumors are rare central nervous system neoplasms characterized by mixed neuronal and glial components, predominantly affecting pediatric and young adult populations. This article provides an in-depth analysis of glioneuronal tumors, emphasizing neuroimaging findings critical for diagnosis, differential diagnosis, and surgical planning. MR imaging remains the cornerstone, with advanced techniques like perfusion and functional MR imaging offering additional insights. Prognosis is generally favorable for low-grade tumors, though high-grade variants pose challenges. Innovations in radiomics, molecular profiling, and personalized medicine are transforming management. This article synthesizes current knowledge, highlighting imaging's pivotal role, and future directions.

Advances in molecular and genomic testing have not only discriminated pediatric from adult high grade gliomas but also distinguished new entities in this family, 3 of which are new to the classification. We have reviewed the published literature to date and present the characteristic and most common findings of each type on structural MR imaging, as well as advanced imaging, where available. Prognostic features, particularly in diffuse midline gliomasK27a have also been described, in addition to practice recommendations.

Pediatric diffuse low-grade gliomas (LGGs) are heterogeneous group of central nervous system tumors that typically exhibit a relatively benign clinical course. These tumors represent a unique classification in pediatric neuro-oncology, distinct from adult counterparts in terms of biological behavior, molecular pathways, and clinical presentation. The evolving World Health Organization classification system has increasingly relied on combination of histopathologic, genetic, and radiologic criteria to define and distinguish among pediatric glioma subtypes. This article aims to synthesize current knowledge regarding the clinical, molecular, and radiologic features of these pediatric diffuse LGGs and highlights the nuances in diagnosis, treatment approaches, and prognostic outlook.

The last decade has seen major advances in our understanding of the biology of pediatric brain and spinal cord tumors and why they are fundamentally different from their adult counterparts. Many of these advances have been adapted into the latest WHO classification of tumors of the central nervous system. This article summarizes the major changes to the WHO classification in this area, highlighting the key histopathologic and molecular features of these new entities.

Published in 2021, the 5th edition of the World Health Organization central nervous system tumor classification introduced major changes to the categorization of pediatric brain and spinal cord tumors. Greater focus has been placed on the integration of molecular genetics, highlighting its emerging importance in the diagnosis, prognostication, and targeted therapy of these tumors. New molecularly defined tumors, reclassification of existing tumors, and revised nomenclature are discussed in this article, and subsequent articles provide further information on this new central nervous system tumor landscape in pediatric neuroradiology.

Computer-aided diagnosis using deep learning has emerged as a transformative tool in pathology that enables the automated and consistent interpretation of whole slide images. Among the key tasks in pathological image analysis, classification-based deep learning models have shown promise in distinguishing cancer subtypes and predicting genetic or molecular features. However, challenges remain due to the limited availability of high-quality labeled datasets, particularly for rare cancers, which hinders the widespread applicability of conventional data-driven approaches.