Advanced cholangiocarcinoma harbors various genetic alterations, one of the most common being fibroblast growth factor receptor (FGFR) fusions. Although FGFR inhibitors have a good response rate, their median progression-free survival is about 6 - 9 months in most trials. The present manuscript is a non-systematic review that explores the mechanisms of resistance and the possible strategies to overcome this rapid resistance. From the findings, resistance to FGFR inhibition can be classified into either primary or secondary resistance. Primary resistance is less common, explained mostly by the presence of co-mutations. In contrast, secondary resistance mechanisms are similar to other tyrosine kinase inhibitors: On-target mutations alter the binding site of the FGFR protein (gatekeeper resistance); off-target mechanisms are multifactorial and involve the activation of related intracellular pathways and the loss of differentiation, leading to a mesenchymal phenotype. Various strategies are in development in order to maintain the efficacy of targeted therapy for patients by overcoming FGFR inhibition resistance, including the coinhibition of the related pathway, the use of pan-FGFR inhibitors, and the development of covalent or dual FGFR inhibitors.

Despite advancements in diagnostic and therapeutic strategies, early detection and improved prognosis of gliomas remain challenging. A deeper understanding of glioma pathogenesis and the identification of reliable biomarkers are crucial for early diagnosis and the reduction of healthcare costs. Mitochondrial ribosomal protein S33 (MRPS33), a key component of mitochondrial protein synthesis, has not been well-characterized in terms of its expression profile, prognostic significance, and immunological relevance in glioma. This study aims to elucidate these aspects through bioinformatics analyses utilizing data from The Cancer Genome Atlas, Genotype-Tissue Expression Project, and Tumor Immune Estimation Resource databases through the Sangerbox platform. Our results indicate a pronounced upregulation of MRPS33 in glioma tissues, which is significantly associated with poor prognosis, heightened immune cell infiltration, and differential drug sensitivities. Furthermore, functional enrichment analyses suggest that MRPS33 is intricately involved in several key biological processes, thereby underscoring its potential role in glioma pathophysiology. In conclusion, our findings support the potential of MRPS33 as a prognostic biomarker and therapeutic target in glioma, providing insights that may advance our understanding of disease mechanisms and inform future clinical strategies.

Triple-negative breast cancer (TNBC) is an aggressive and metastatic form of breast cancer with limited treatment options. Glycolytic enzymes such as hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA) serve as effective targets for metabolic reprogramming in suppressing tumor growth. This study investigates the effects of glycolytic enzyme inhibitors, particularly phytochemicals, on TNBC metastasis and tumor growth using a 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat model. Following TNBC induction, these rats were treated with phytochemical inhibitors: 2-deoxy-D-glucose (2-DG), shikonin, oxamate, kaempferol, quercetin, or luteolin. Molecular docking analysis was conducted to characterize the interactions between these compounds and the glycolytic enzymes HK2, PKM2, and LDHA. Glycolytic enzyme inhibition was inferred from the protein expression levels of HK2, PKM2, and LDHA in different treatment groups. Among the compounds tested, kaempferol showed the highest binding affinity toward glycolytic enzymes HK2 and PKM. In addition, shikonin and kaempferol exhibited cell-line-specific antiglycolytic properties by inhibiting glycolytic enzymes HK2, PKM2, and LDHA, thereby suppressing TNBC growth and metastasis. These results suggest that glycolytic enzymes could serve as potential therapeutic targets for improving TNBC treatment, with possible clinical application alongside primary conventional therapies.

Colorectal cancer (CRC) has been associated with metabolic and inflammatory dysregulation, particularly in lipid and glucose metabolism. This study investigates the role of serum lipids and biochemical markers as potential biomarkers for CRC in the South Indian population. A case-control observational study was conducted involving 65 CRC patients and 65 age- and sex-matched healthy controls. Participants were selected based on strict inclusion and exclusion criteria, ensuring the elimination of confounding factors such as other malignancies or chronic conditions. Blood samples were analyzed for lipid profiles, high-sensitivity C-reactive protein (hs-CRP), and other biochemical parameters using enzyme immunoassay kits. Statistical analyses were performed to evaluate differences between groups, with a p<0.05 considered statistically significant. Significant elevations in total cholesterol (TC), low-density lipoprotein (LDL), and the TC/high-density lipoprotein (HDL) and LDL/HDL ratios were observed in CRC patients compared to controls. The observed high hs-CRP levels indicate the heightened inflammatory state in CRC. The levels of triglycerides, HDL, and very-LDL showed no significant differences, although trends of elevated uric acid and urea levels in CRC patients were noted. Blood glucose levels were significantly higher in CRC patients, suggesting possible disruptions in glucose metabolism. Liver and renal function markers remained within comparable ranges across both groups. The study highlights dysregulated lipid and glucose metabolism and increased inflammatory markers in CRC patients from the South Indian population. Elevated LDL, TC, and hs-CRP may serve as potential biomarkers for early detection and risk assessment in CRC. These findings highlight the importance of monitoring lipid and glucose profiles in CRC patients and pave the way for further research into their role in CRC pathogenesis and progression.

Classical Hodgkin lymphoma is a highly curable malignancy, but long-term treatment-related toxicities remain a challenge, especially in young survivors. In recent years, treatment has shifted from traditional doxorubicin, bleomycin, vinblastine, and dacarbazine regimens to novel approaches such as positron emission tomography-guided therapy, brentuximab vedotin-doxorubicin, vinblastine, dacarbazine (AVD), and checkpoint inhibitor combinations such as nivolumab (Nivo)-AVD. This review evaluates these three frontline strategies in terms of efficacy, toxicity, and their potential to personalize treatment and minimize late complications. Drawing from trials such as ECHELON-1, NIVAHL, SWOG S1826, and BREACH, we analyze current evidence, evaluate conflicting data, and propose considerations for tailoring therapy to patient subgroups.

This case report highlights the diagnostic challenges and therapeutic considerations when dermatofibrosarcoma protuberans (DFSP) present in atypical locations, such as the head and neck. A 46-year-old Hispanic male presented with a large, rapidly growing, protruding mass on the left medial forehead, initially diagnosed through ultrasound as a benign cyst. The lesion exhibited a significant increase in size over 5 months. Physical examination revealed a firm nodular mass without signs of inflammation or lymphadenopathy. The lesion was excised for biopsy, and histopathological analysis confirmed a diagnosis of DFSP, characterized by spindle cells arranged in a storiform pattern. Immunohistochemical staining revealed strong CD34 positivity, with negative markers for desmin, factor XIIIa, and SOX10. The tumor exhibited an infiltrative pattern, extending into the skeletal muscle. The patient was referred for wide local excision due to the complexity of achieving clear margins in a cosmetically sensitive area such as the forehead. DFSP most commonly occurs on the trunk and proximal extremities, with less frequent involvement of the head and neck. This case is notable for its atypical location on the forehead, making surgical excision particularly challenging due to the need for margin control while preserving facial esthetics. Initial misdiagnosis as a benign cyst highlights the diagnostic difficulty of DFSP in uncommon locations. The tumor’s rapid growth and deep infiltration into skeletal muscle are further complicated management, requiring careful surgical planning to prevent a recurrence. Long-term follow-up is essential due to the high recurrence rate of DFSP when margins are inadequate.

Despite advancements in medical technology, cancer remains a leading cause of mortality, with colorectal cancer consistently ranking among the most prevalent cancers worldwide. Diet can either contribute to or protect against the development of cancer. The Asian region is known for its extensive consumption of fermented foods, which may influence colorectal cancer due to the diverse range of microorganisms and compounds produced during fermentation. These components can affect the tumor microenvironment, potentially leading to either beneficial or adverse effects on colorectal cancer.