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.

Cisplatin-induced ototoxicity (CIO) is a serious and underrecognized side effect of chemotherapy that, for various reasons, is often overlooked or omitted from focused care discussions between oncology providers and patients.

Chemotherapy-induced neutropenia is a frequent complication in patients with cancer that can lead to severe outcomes like sepsis, hospitalizations, and treatment delays. A neutropenic sepsis care bundle was implemented in an.

At diagnosis and throughout treatment of acute myeloid leukemia, oral leukemic infiltrates from malignant blast cell invasion and mucosal ulcerations (i.e., mucositis as a side effect of antineoplastic therapy) are common. Ma.

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.

Pancreatic cancer remains largely refractory to immune checkpoint inhibitors. High-intensity focused ultrasound (HIFU) may modulate the immunosuppressive tumor microenvironment via immunogenic cell death, yet clinical evidence on HIFU combined with programmed cell death protein 1 (PD-1) inhibitors in elderly patients is scarce.

The gut microbiome shapes chemotherapy efficacy and outcomes in several cancers, but evidence in ovarian cancer (OC) remains limited and largely cross-sectional. Despite high initial response rates, long-term relapse in OC remains frequent, while conventional markers capture only short-term therapeutic sensitivity. Whether longitudinal gut-microbiome trajectories during chemotherapy are associated with long-term recurrence remains unknown.

Two series of 1,2,3-triazole-based molecules were synthesized. Their physical properties were documented, and cytotoxicity was evaluated against normal lymphocytes, leukemic, adherent, and nontumor cell lines. Compounds 11, 15, and 16 were inactive, while compound 17 affected both normal and cancer cells. Compounds 18 and 20 showed activity against BJ and A549 cell lines, with compound 20 being selective for T-cell leukemias and compound 18 moderately affecting B-cell leukemia. Compound 12 specifically affected the HCTp53 KO cell line, while compounds 13 and 14 were selective for U2O2 and HCT116 cell lines, respectively. Compound 14 was highly specific for T-cell leukemia, whereas compound 19 was specific for A549 and moderately specific for B-cell lines. Compound 22 affected all tumor cell lines except A549. The active compound induces apoptosis since it activates caspase 3. Spheroid testing revealed that compounds 13 and 22 specifically affected HCT116 spheroids, while compound 19 affected A549 spheroids. Both in vitro and computational analyses demonstrated that compounds 11, 12, and 13 exhibit high affinity for the A Cα subunit of protein kinase A. This suggests a kinase-targeted mechanism of action, providing a structural foundation for future design strategies to optimize the potency of these lead compounds.

Lung squamous cell carcinoma (LUSC) is a difficult cancer to treat, with few targeted therapies to improve its poor prognosis. The goal of this study was to use a drug repurposing strategy to evaluate and compare drug sensitivities using 2D adherent and 3D spheroid models of NCI-H2170 LUSC cells. Both 2D adherent and 3D spheroid models were used to grow NCI-H2170 lung squamous cell carcinoma cells and evaluate their sensitivity to a large library of food and drug administration (FDA)-approved drugs, including many not typically used as anti-cancer agents. Cell death was assessed in the 2D adherent models, and for the top drugs half maximal effective concentration (EC50) values were determined. For the 3D spheroid models, drugs reducing spheroid size after 4 days of treatment were identified. There were 263 drugs that reduced the cell viability to <20% when cells were grown in 2D in 10 µM drug. When grown in 3D the cells were generally more drug resistant, with 87 drugs capable of reducing spheroid volume when grown over 4 days in 10 µM drug. Interestingly, 60 drugs proved effective in both model systems including many drugs that typically associated with anti-cancer properties. Of these 60, four were further found to have selective effects towards metastatic NCI-H2170 cells as compared to a much less metastatic matched cell line expressing the metastasis suppressor CREB3L1, in both 2D and 3D model systems. These included the hypoxia-inducible factor 1-alpha (HIF-1α inhibitor 2-methoxyestradiol, and three anti-infection agents (cetylpyridinium chloride, chlorhexidine-2HCl, zinc pyrithione).

The elevated mortality associated with ovarian cancer arises from delayed detection, recurrent disease, and the rapid emergence of chemoresistance. This study assesses the anticancer efficacy of two synthetic curcumin analogues, B-143 and B-155, in comparison to natural curcumin, employing SKOV3 ovarian cancer cells as the experimental model.

Recent studies have shown that while chemotherapy kills tumor cells, it may also induce adaptive changes in cells within the tumor microenvironment, particularly cancer-associated fibroblasts (CAFs), which could paradoxically promote tumor progression. This study aimed to investigate the role of CAFs exposed to paclitaxel (PTX) or doxorubicin (DOX) in tumor progression and explore the underlying mechanisms.

Cancer remains one of the leading causes of mortality worldwide. Dysregulated cellular signaling pathways play a pivotal role in tumorigenesis, tumor progression, and metastasis. Among these, tyrosine kinases (TKs) constitute a critical class of enzymes that catalyze the phosphorylation of tyrosine residues on target proteins, thereby regulating key cellular processes including growth, differentiation, and survival. TKs have revolutionized cancer therapy by selectively targeting these enzymes, resulting in suppressed tumor growth and improved clinical outcomes for patients. Urea-containing motifs represent one of the most important bioactive functional groups in medicinal chemistry. In particular, unsymmetrical alkyl- and benzylureas are widely employed as key structural components in numerous approved drugs. This structural feature enables versatile modifications that enhance physicochemical properties, including solubility, metabolic stability, and bioavailability. This review explores the current landscape of antineoplastic urea-based tyrosine kinase inhibitors, presenting an exhaustive examination of contemporary urea-containing compounds that inhibit TKs while elucidating their mechanisms of action and molecular targets. In recent years, computational technologies have become indispensable in modern drug discovery. They significantly accelerate the identification of new TKIs and support the repurposing of established pharmaceuticals. Ultimately, the review addresses the prevailing challenges and future opportunities in the advancement of urea-containing tyrosine kinase inhibitors.