Triple negative breast cancer (TNBC) and ovarian cancer share many molecular features and are primarily treated with surgical resection and aggressive chemotherapy regimens. Unfortunately, survival rates for patients with advanced metastatic disease are poor, highlighting the need for innovative therapeutic approaches.

Pathological ocular neovascularization is a major driver of vision-threatening retinal diseases. This study aimed to investigate the role and therapeutic potential of miR-15a-5p in ocular neovascular disorders.

Immune checkpoint inhibitors (ICIs) have revolutionized lymphoma treatment, yet resistance driven by complex regulatory networks remains a major hurdle. Circular RNAs (circRNAs) have emerged as central signaling hubs that integrate metabolic, inflammatory, and oncogenic cues to fine-tune immune checkpoints such as PD-L1 and CD47 in lymphoma. Here, we systematically dissect the molecular mechanisms by which circRNAs govern immune checkpoints in lymphoma, including nuclear transcriptional control, interactions with RNA-binding proteins (RBPs), competitive endogenous RNA (ceRNA) networks, and micropeptide translation. We differentiate between cell-extrinsic, exosome-mediated reprogramming of the tumor microenvironment and cell-intrinsic circRNA circuits within lymphoma cells spatially. Subtype-specific investigations demonstrate the importance of Epstein-Barr virus (EBV)-encoded circRNAs in immune evasion and the synergistic interactions between 9p24.1 amplification and circRNAs in classical Hodgkin lymphoma (cHL). While therapeutic approaches including antisense oligonucleotides, CRISPR-Cas13, and nanodelivery technologies demonstrate preclinical synergy with ICIs, circulating circRNAs show potential as dynamic indicators for predicting ICI responses. We also critically examine ongoing discussions about the flaws of current model systems, the technological constraints of current validation techniques, and the physiological significance of the ceRNA hypothesis. Positioning circRNAs as multimodal regulatory hubs, this review provides a theoretical framework for developing circRNA-based immunotherapies to overcome resistance in lymphoma.

Nucleolar Protein 14 (NOP14), a highly conserved factor in eukaryotes, is essential for pre-18S rRNA processing and small ribosomal subunit assembly. Emerging evidence underscores its pivotal regulatory role in the progression of various malignancies. Nevertheless, its functional involvement in Diffuse large B-cell lymphoma (DLBCL), particularly its capacity to modulate the tumor immune microenvironment, remains to be fully elucidated.

Mitotane remains the cornerstone of adrenocortical carcinoma. However, its real-world safety profile is poorly defined. This study systemically evaluated mitotane-associated adverse events (AEs) and characterized multivariable patterns of serious outcomes using a combined pharmacovigilance and machine learning approach.

Glioblastoma (GB) is the most aggressive primary malignant brain tumor in adults and remains associated with poor survival despite surgical resection followed by radiotherapy and temozolomide (TMZ) chemotherapy. Intrinsic and acquired resistance to TMZ, including MGMT-dependent DNA repair and activation of pro-survival pathways, could decrease treatment efficacy. Drug repurposing offers an attractive strategy to identify agents that may enhance TMZ activity because these drugs already have known pharmacokinetic and safety profiles. This narrative review summarizes the available evidence on repurposed drugs investigated as potential modulators of TMZ response in GB.

The expanding clinical use of Antibody-Drug Conjugates (ADCs) necessitates a clearer understanding of their real-world toxicity profiles across diverse clinical settings. This retrospective pharmacovigilance study analyzed 19,697 adverse event (AE) reports for seven approved ADCs from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q1 2025). Using disproportionality analysis validated by multivariable logistic regression, we identified safety signals for both monotherapy and combination regimens. The analysis revealed that toxicity profiles are strongly driven by an ADC's molecular structure and treatment setting. Target-specific 'on-target, off-tumor' effects were prominent, linking Nectin cell adhesion molecule 4 (NECTIN-4) targeting to skin reactions, Trophoblast cell-surface antigen 2 (TROP2) to gastrointestinal toxicities, and both folate receptor α (FRα) and tissue factor (TF) to ocular disorders. Furthermore, payload and linker types drove distinct toxicities; topoisomerase I inhibitors were associated with increased respiratory toxicity and mortality, while non-cleavable linkers conferred a significantly stronger risk of hepatobiliary toxicity. Combination regimens not only amplified specific risks, such as endocrine disorders with immune checkpoint inhibitors (ICIs), but also fundamentally reshaped toxicity kinetics, accelerating AE onset with ICIs while significantly delaying it with other combinations. This real-world analysis confirms that ADC toxicities are highly specific to their molecular design and clinical context, highlighting that understanding these complex structural and kinetic interplays is essential for optimizing safety management in clinical practice.

Prostate cancer (PCa) is one of the most common cancers in males, and its treatment remains challenging due to the tumor microenvironment (TME) with immunosuppressive properties and limited response to anti-PD-1 therapy. Gut microbiota-derived metabolites have recently emerged as modulators of cancer immunometabolism, however, their role in PCa progression and immunotherapy is poorly understood. Here we found that indole-3-lactic acid (ILA), a metabolite produced by Lactobacillus plantarum, exerted dual anti-tumor effects on PCa cells and the TME. Mechanistically, ILA activates the aryl hydrocarbon receptor (AHR), and the resulting AHR/ARNT heterodimer translocates into the nucleus and binds to the promoter of ASF1B. This heterodimer then recruits the HDAC1/2-NuRD complex to reduce H3K27ac levels and suppress ASF1B expression. ASF1B binds to specific residues of ENO1 via its N-terminal core domain and enhances ENO1 enzymatic activity. ILA-induced downregulation of ASF1B impairs this interaction, reduces ENO1 activity, and suppresses the PI3K/Akt pathway, thereby inhibiting the malignant phenotypes of PCa cells. Concurrently, ILA decreased CXCL8 secretion by inhibiting the PI3K/Akt/NF-κB pathway, enhancing CD8+ T cell infiltration and M1 macrophage polarization, thereby remodeling the TME. Additionally, ILA synergized with anti-PD-1 therapy to more effectively suppress tumor growth. These findings reveal a novel mechanism by which gut microbiota-derived metabolites regulate PCa progression and immunometabolism, positioning ILA as a potential therapeutic agent to improve PCa treatment.

An encrusting, algae-associated octocoral, Briareum stechei, afforded three 8,17-epoxybriarane diterpenoids, including the known compound briaexcavatolide B (1) and two previously undescribed analogues, briastecholides Q (2) and R (3). The absolute configuration of 1 was established for the first time by single-crystal X-ray diffraction analysis. The planar structures and relative configurations of 2 and 3 were determined through extensive spectroscopic analyses. In bioactivity evaluation, compound 2 exhibited cytotoxic effects toward the human acute lymphoblastic leukemia cell lines Molt-4 and CCRF-CEM.

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and is often diagnosed at an intermediate stage in patients with chronic liver disease. Transarterial chemoembolization (TACE) is the first-line treatment in this setting. However, drug response remains variable and optimal chemotherapeutic selection unresolved. Idarubicin (IDA) has previously demonstrated antitumor activity comparable to doxorubicin (DOX), with improved emulsion stability and membrane permeability. 3D patient-derived organoids (PDOs) have also recently emerged as physiologically relevant systems that recapitulate tumor characteristics and inter-patient heterogeneity more accurately than conventional 2D cell cultures. In this study, we characterized HCC PDOs and investigated their utility as an ex vivo model to assess therapeutic responses. We generated organoids from tumor and non-tumor liver biopsies collected from HCC patients prior to TACE-treatment. PDOs partially preserved tumor architecture and phenotypic features. IDA exposure resulted in a concentration-dependent reduction in organoid growth, with marked inter-patient variability in drug response. Comparative analyses showed that IDA was more potent than DOX, with lower IC₅₀ values across all patient-derived samples. IDA also induced transcriptional changes associated with cellular stress, inflammation, and proliferation pathways. However, ex vivo drug‑sensitivity testing in PDOs did not correlate with clinical response to TACE. These findings confirm the feasibility of generating HCC PDOs and using them to evaluate differential sensitivity to TACE‑associated chemotherapeutic agents ex vivo, although their ability to predict clinical efficacy remains unproven. While IDA exhibited greater cytotoxic activity than DOX in organoid cultures, this observation was based on in vitro sensitivity assays and does not establish clinical superiority. Furthermore, the absence of correlation between PDO drug sensitivity and clinical TACE response indicates that PDO-based prediction of treatment outcome remains challenging in this setting.

Chalcones (1,3-diphenyl-2-propen-1-one) are open-chain flavonoids recognized for their structural diversity and broad pharmacological activities. Electrophilic α,β-unsaturated carbonyl systems and versatile substitution patterns on aromatic rings have positioned the chalcones as privileged structures in medicinal chemistry. This review highlights the contributions of Brazilian investigations to the advances of chemistry and bioactivity of natural and synthetic chalcones over the last 40 years. A systematic search of PubMed, Scopus, Embase, and Web of Science up to February 2026 identified 661 publications, revealing a growing interest since the early 2000s and reflecting the consolidation of chalcone as a central subject of research groups. Brazilian investigations have shown chalcones as antibacterial, antifungal, antiparasitic, anticancer, and anti-inflammatory agents, affording pivotal insights into structure-activity relationships and mechanisms of action at the molecular level. In addition, we submitted the most active chalcones to in silico evaluations, using SwissADME web tool, allowing a comparative analysis of their physicochemical, pharmacokinetics, and drug-likeness properties. The results indicated the majority of these compounds demonstrated an appropriate drug-like behavior. Collectively, the set of findings has positioned Brazil as an important research powerhouse of chemistry and pharmacology of chalcone and its derivatives, which may impact the discovery of innovative therapeutic agents.

Ultrasmall cyclodextrin-based nanogels (CDngs) crosslinked with ethylene glycol diglycidyl ether (EGDE) were tested as drug delivery systems for poorly water-soluble anticancer agents for the first time. Two compounds with well-established pharmacological activity but critical solubility limitations, i.e., Osthole and Combretastatin A-4 (CA-4), were selected to evaluate the encapsulation capacity and performance of the nanogel platform. After preliminary screening through experimental and docking investigation, CA-4 was chosen as the reference compound. Among the formulations developed, the CA-4/loaded nanogel displayed the highest encapsulation efficiency (EE%). Despite a less-than-ideal host-guest fit, the large cavity of γ-CD allows for efficient drug encapsulation and higher loading capacity. The optimized formulation was tested in vitro to assess both the biocompatibility of γ-CDngs, as well as the anticancer efficacy of CA-4 loaded γ-CD and γ-CDngs. We demonstrate that empty systems exhibit intrinsic biocompatibility, showing no cytotoxicity toward the A2780 cancer cell line under experimental conditions. Furthermore, the CA-4 loaded γ-CDngs retained and enhanced the cytotoxic properties of the free drug against this cell line, compared to the corresponding native γ-CD. Collectively, these findings validate CDngs as a promising and innovative platform for the delivery of hydrophobic anticancer molecules and support their potential for further therapeutic development.

Natural and synthetic protoflavonoids exhibit a wide range of anticancer activities, including strong antiproliferative, proapoptotic, and DNA damage response-inhibitory activities; however, the surrounding chemical space has remained largely unexplored. In this study, we report the synthesis and biological evaluation of a focused compound library containing the p-hydroxydienone pharmacophore of protoflavonoids. Eleven derivatives were synthesized and characterized from chalcone precursors, and their antiproliferative activity was evaluated in four human adherent gynecological cancer cell lines (MCF-7, MDA-MB-231, HeLa, and SiHa). The investigated compounds exhibited mild to strong activity, with several showing notable selectivity for triple-negative MDA-MB-231 cells. Our findings suggest that the unexplored chemical space around protoflavonoids might encompass compounds with valuable bioactivity and warrant further research.

The acidic tumour microenvironment (pHe 6.5-6.9) is sustained by the Warburg effect and pH regulators, such as monocarboxylate transporters 1 and 4, Na+/H + exchanger 1, vacuolar ATPase, and carbonic anhydrases IX and XII. This environment facilitates tumour invasion, immune evasion, and resistance to therapy in solid tumours. Recent advancements in small molecule inhibitors targeting these pathways have demonstrated potential in molecular design, mechanisms of action, and preclinical studies. However, practical applications face challenges, including metabolic compensation, insufficient target selectivity, and clinical translation difficulties. This article reviews the structural design, structure-activity relationships, biological activity, and clinical trial progress of small molecule inhibitors. It also summarises acid-targeted delivery strategies, such as pH-responsive prodrugs and pHLIP peptides. The aim is to highlight the opportunities and challenges in acid-base regulation within the tumour microenvironment and offer insights for developing a new generation of antitumor drugs with high selectivity and low toxicity.

Therapeutic resistance remains a major challenge in cancer treatment, driven by compensatory signaling and stress response pathways that sustain tumor survival. Topoisomerase IIβ-binding protein 1 (TopBP1), a multifunctional scaffold protein with nine BRCT domains, integrates replication stress signaling with oncogenic networks and is frequently overexpressed in aggressive cancers. Its BRCT7/8 domains mediate critical interactions with E2F1, mutant p53, MIZ1, PLK1, and CIP2A, making TopBP1-BRCT7/8 an attractive therapeutic target. Using docking-guided screening and structure-activity relationship-driven optimization, we developed CS18 as a potent and selective BRCT7/8 inhibitor that disrupts oncogenic TopBP1 complexes without interfering with DNA replication. CS18 suppresses MYC transcriptional programs, restores E2F1-mediated apoptosis, and induces mitotic catastrophe. It exhibits broad-spectrum anticancer activity and synergizes with poly(ADP-ribose) polymerase (PARP) inhibitors in multiple cancer types and enhances osimertinib sensitivity in EGFR-mutated non-small cell lung cancer (NSCLC) cells. CS18 demonstrates efficacy in patient-derived breast cancer xenografts and overcomes osimertinib resistance in refractory NSCLC in vivo. These findings establish CS18 as a chemically distinct TopBP1 inhibitor with translational potential to overcome therapeutic resistance and advance precision oncology.

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet cancer-related fatigue (CRF) remains a frequent but poorly characterized adverse effect. We evaluated CRF incidence during ICI treatment in neoadjuvant and adjuvant settings.

This study aimed to systematically synthesize and separately quantify the pooled safety profiles of bispecific antibodies (BsAbs) targeting PD-1/CTLA-4 or PD-1/VEGF in patients with non-small cell lung cancer (NSCLC), and to descriptively summarize class-specific safety patterns.

Chemotherapy drugs are hazardous and require strict safety protocols to protect health care workers. In the Gaza Strip, cancer is a leading cause of death, yet there is limited research on nurses' adherence to safe chemotherapy handling practices. This study assesses the safe chemotherapy handling behaviors of nurses at the Turkish Palestinian Friendship Hospital in Gaza.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies to date and characterized by a unique immunosuppressive and highly desmoplastic tumor microenvironment (TME). These features drive profound T-cell dysfunction and maintain high resistance to current immunotherapy. By recapitulating the complex 3D architecture of human PDAC, we demonstrate the key immunosuppressive mechanisms that drive T-cell dysfunction within the tumor microenvironment.

To perform signal mining of neuro-ophthalmic immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) using the FDA Adverse Event Reporting System (FAERS), and to synthesize their clinical manifestations and temporal patterns, thereby providing evidence-based insights for optimizing clinical drug safety.