Near-infrared (NIR) light-responsive nanomaterials have emerged as powerful tools for cancer therapy, yet stable and biocompatible delivery of NIR-II agents remains a major challenge. In this work, we develop NIR-I/II-responsive niosomes co-encapsulating plasmonic gold nanorods (GNRs) and the NIR-II dye, IR1061, forming a multifunctional nanoplatform for effective phototherapeutic ablation of cancer cells. The niosomal system provides robust encapsulation, improved dispersion stability, and biocompatibility for both photoactive components. Upon NIR-I/II laser irradiation, the nanoplatform exhibits strong photothermal heating and substantial reactive oxygen species generation due to the synergistic integration of plasmonic GNRs and dye-mediated effects. In vitro evaluations demonstrate efficient cellular uptake, potent photoinduced cytotoxicity, and minimal dark toxicity. The integration of photothermal and photodynamic mechanisms results in markedly enhanced therapeutic efficacy compared with individual agents. This study highlights the potential of niosomes as versatile and efficient nanocarriers for dual NIR-window phototherapy, offering a promising route for precise and minimally invasive cancer treatment.

Although routine treatment methods aim to aggressively destroy tumour tissues, they often fail to account for the correlations of tissue destruction and regeneration processes. Despite considerable progress in the field of oncology, it is worth noting the ancient ways of treatment using products from nature which potentially can effectively support current therapies.

Over the past decade, antibody-drug conjugates (ADCs) have emerged as promising anti-cancer therapeutics, with twelve ADCs approved by the FDA. This review evaluates trends in these ADCs, stratified by payloads on doses studied from first-in-human (FIH) trials through approval and post-marketing. It summarizes trends in pharmacokinetics (PK), drug-drug interactions (DDI), exposure-response analysis, immunogenicity, and organ impairment. Additionally, it provides perspectives on potential postmarketing requirements associated with clinical pharmacology attributes, and how this knowledge could inform efficient early clinical development of newer ADCs. Except for sacituzumab govitecan, which had a starting dose of 8 mg/kg, starting doses of ADCs ranged from 0.0067 to 0.8 mg/kg. All ADCs have been administered intravenously. Dose escalation generally progressed over four to eight distinct levels, with increments of 20% to 233% at the first three levels. The maximum tolerated dose was achieved by the fourth to seventh dose level in most cases. For 5/12 ADCs, the recommended phase 2 dose and the phase 3 dose were the same as the MTD. Approved doses ranged from 1.25-fold to 40-fold higher than the FIH starting dose levels. Generally, ADCs exhibited dose-proportional PK within the tested dose range. Exposure-response relationships have been reported for ADC/total antibody for efficacy and ADC/total antibody/payload exposures for safety. DDI potential has been reported for payloads associated with auristatins, maytansinoids, and camptothecin: SN38. At approved doses, immunogenicity assessments indicated low incidence of anti-drug antibodies. Organ impairment studies suggest no significant risk in patients with moderate hepatic or renal impairment.

Herein, we described the design and synthesis of a series of melampomagnolide B-dithiocarbamate hybrids and the evaluation of their anti-lung cancer activities. The most active compound 86 (IC50 = 0.46 μM) exhibited a highly potent inhibitory effect on NCI-H820 cells, with a 44-fold increase compared to the natural product melampomagnolide B (IC50 = 20.43 μM). Compound 86 mediated mitochondrial dysfunction, promoted ROS generation to disrupt redox homeostasis, and eventually induced apoptosis, ferroptosis, and cuproptosis in lung cancer cells in vitro and in vivo. Preliminary toxicity assessment indicated that compound 92, the water-soluble prodrug of 86, exhibited no apparent toxicity. Furthermore, 92 significantly reduced the tumor volume and tumor weights in lung cancer CDX and PDX models. These findings suggested that 92 deserved further studies as a potential candidate for the ultimate discovery of effective anti-lung cancer agents.

Breast cancer remains one of the most common malignancies affecting women worldwide. Despite the effectiveness of traditional chemotherapeutic agents such as 5-fluorouracil (5-FU), their lack of selectivity often results in damage to healthy tissues, leading to undesirable adverse effects. The aim of this study was to modify 5-FU with mannose containing 1,2,3-triazole compound to reduce its toxic effect, and to investigate the anticancer properties of the resulting 5-FU derivative (5-FUD-Man) in ER-positive MCF-7 breast cancer cells. Our results demonstrated that while 5-FU caused significant cytotoxicity in both cancerous and healthy cells, 5-FUD-Man showed selective cytotoxicity, with minimal effects on MCF-10A cells. Furthermore, immunofluorescence staining results indicated that 5-FUD-Man was more strongly activated apoptosis (Caspase-3, AIF), autophagy-mediated (LC3B), and stress-associated signaling pathways (ERK1/2) in MCF-7 cells compared to 5-FU. These findings suggest that the combined use of carbohydrate-based targeting via mannose and a bioactive triazole compound may enhance the selectivity and therapeutic efficacy of 5-FU-based treatments in breast cancer. Overall, 5-FUD-Man appears to be a promising candidate for further development as a more targeted and potentially safer therapeutic strategy.

A new series of aliphatic-substituted benzimidazole derivatives was synthesized and structurally characterized to evaluate their potential anticancer activity. Among the synthesized compounds, compound 4 exhibited the most potent cytotoxic effects against MCF-7 and MDA-MB-231 breast cancer cell lines, with IC₅₀ values comparable to those of cisplatin, while displaying lower toxicity toward normal breast epithelial cells (MCF-10A). Flow cytometric analysis revealed that treatment with compound 4 resulted in significant accumulation of cells in the S phase, indicating inhibition of DNA synthesis and replication. Furthermore, Annexin V/PI double-staining analysis demonstrated a marked increase in both early and late apoptotic cell populations, confirming the activation of apoptotic pathways. Molecular docking studies supported these experimental findings by revealing strong interactions of compound 4 with key regulatory proteins involved in apoptosis and cell cycle progression, including Bcl-2, Bcl-xL, CDK2, and Cyclin E. The compound exhibited the highest binding affinity toward CDK2 (-164.055 kcal/mol), forming hydrogen bonds with critical residues (LEU134, ASP145, GLN131, and LYS33) within the ATP-binding pocket, suggesting potential inhibition of kinase activity. Interactions with Bcl-2 and Bcl-xL occurred within the BH3-binding grooves, which may impair their anti-apoptotic functions and promote mitochondrial-mediated apoptosis. Collectively, the in vitro and in silico results indicate that this newly synthesized benzimidazole derivative exerts its anticancer effects through a dual mechanism involving cell cycle arrest and apoptosis induction. The selective cytotoxicity and multitarget interaction profile of compound 4 highlight its potential as a promising lead compound for the development of novel therapeutic agents against breast cancer.

Multi-target enzyme inhibition represents a promising strategy to overcome resistance and improve therapeutic outcomes in cancer therapy. In this study, a new series of 1,3,4-oxadiazole derivatives was synthesized and evaluated for cytotoxic and multi-target anticancer activities. Several compounds demonstrated potent antiproliferative effects against HepG2, MCF-7, and HCT-116 cancer cell lines with reduced toxicity toward WI-38 normal fibroblasts. Among them, compounds 1, 9, 12, and 13 emerged as the most promising candidates, showing strong cytotoxicity and favorable selectivity profiles. Enzyme inhibition assays confirmed their ability to target key oncogenic enzymes, including wild-type and mutant (T790M) EGFR, telomerase, and thymidylate synthase. Mechanistic studies revealed that compound 12 induced G1 phase cell cycle arrest and promoted apoptosis in HepG2 cells with minimal necrosis. Molecular docking, molecular dynamics simulations, and MM-GBSA analyses supported stable binding of the active compounds within the catalytic sites of the investigated enzymes. Overall, these findings identify compounds 1, 9, 12, and 13 as promising multi-target anticancer leads warranting further optimization and development.

The current thiazole Schiff base ligand was obtained upon reacting 2-amino-5-methylthiazole with 2,4-dihydroxybenzaldehyde (H2L). The transition metal chelates then were presented by reacting the ligand with Mn(II), Cu(II), and Zr(IV) salts in 1:1 molar ratio forming chelates, 1, 2 and 3, respectively. The reaction of the ligand with Cd(CH₃COO)₂ afforded Cd(II) complex, 4, in the molar ratio 2L:1 M. The type of contact that occurs between metal ions and the thiazole ligand was investigated by the assistance of magnetic susceptibility, FTIR, mass, UV-Visible and 1H NMR spectral and micro-elemental analyses. The resulting data demonstrated that the ligand-metal interaction happened via the phenolic O-atom ortho-position and the imine group N- atom which is dehydrogenated to form the metal complexes. Solvent molecules attached to the metal ions in complexes, whether present or absent were suggested using TGA in addition to thermodynamic activation parameters for the thermal decomposition steps were computed by the Eyring equation. Magnetic moment and UV-Visible measurements indicated formation of square planar Cu(II) chelate and octahedral Zr(IV) chelate, while the Mn(II) and Cd(II) ions formed tetrahedral metal chelates. XRD and TEM used to reveal structural microcrystalline data of both the organic compound (H2L) and inspected complexes. The patterns of X-ray diffraction introduced the crystalline nature of each of the free ligand, complexes 1, 3 and 4, whereas complex 3 was relatively amorphous without an even dispersion of the solid constituents throughout the precipitation procedure. The study rigorously analyzed molecular structures using Density Functional Theory (DFT) calculations, revealing significant variations in ligand bond lengths and angles upon complexation, and demonstrating the electron-donating and accepting properties of HOMO and LUMO orbitals. Biological activity for the prepared compounds was accomplished. They exhibited high activity, especially after chelation. The Antimicrobial activity afforded very auspicious data upon comparison with the applied reference antibiotic. The greatest anti-cancer activity has been achieved by Cu(II)-complex 2 which showed IC50 value = 16.89 µg/ml against MCF-7 cell lines which is greater than the IC50 value of scaled drug applied (IC50 of 5-flurouracil = 28.0 µg/ml). Promising bioactive compounds' binding affinities with HepG-2 and MCF-7 DNA helices were estimated to apply molecular docking.

Immune checkpoint inhibitors have become one of the pillars of cancer treatment, but may be associated with a wide range of potential adverse effects. In this review, we discuss the presentation and management of immune-related adverse events according to their severity and organ system involvement. Tables with management guidelines are included.

Quercetin, a plant-derived dietary flavonoid, has multifunctional biological activities, including anticancer action; however, its applications may be restricted due to limited bioavailability. Thus, novel synthetic quercetin derivatives (QDs) with improved properties and/or drug combinations should be designed and tested. In the present study, anticancer activity of fourteen newly synthesized QDs was investigated using four cellular models of melanoma, namely A375, MM370, G-361, and SH-4 cells. Thioquercetins (thioQ, thioQ(OAc)4, and thioQ(OAc)5), when used at low micromolar range, induced apoptotic cell death in melanoma cells compared to normal cells. Thioquercetins also reduced the population of spheroid-forming cells and suppressed the growth of A375 cells in 3D spheroid models. Thioquercetin-mediated antimelanoma action was potentiated upon heat shock protein 90 (HSP90) inhibition. Co-treatment with the HSP90 inhibitor 17-DMAG and thioquercetins augmented oxidative stress (increased superoxide production, decreased levels of antioxidant proteins SOD1, and PRDX1-2), and impaired the aryl hydrocarbon receptor (AhR)/cytochrome P450 1A1 (CYP1A1) signaling pathway-based detoxification of thioquercetins by the inhibition of AhR translocation to the nucleus and AhR-mediated stimulation of CYP1A1 expression leading to enhanced cytotoxic effects against melanoma cells. The senolytic activity of thioQ(OAc)4 with four acetylated hydroxy groups against cisplatin-induced senescent melanoma cells was also revealed in selected experimental settings. We suggest that the use of novel thioquercetin-based derivatives along with HSP90 inhibitors should be further validated in vivo and considered for the design of more effective antimelanoma strategies in the future.

Immune-mediated diarrhea and colitis (IMDC) is a high-risk toxicity frequently experienced by patients treated with immune checkpoint inhibitors (ICIs) and requiring rapid supportive care interventions. Delays in IMDC reporting and inconsistent guideline adherence increase symptom burden and emergency department (ED) utilization. Although current practice guidelines provide IMDC management recommendations, adherence in routine oncology care remains uncertain. This study evaluated management and guideline concordance for clinically significant IMDC at a single National Cancer Institute-designated comprehensive cancer center to identify workflow opportunities to improve supportive management.

Patients with a DPYD genetic deficiency who receive capecitabine are at increased risk of severe, potentially fatal toxicities due to impaired drug metabolism. Genetic testing for this deficiency allows for proactive dose adjustments to mitigate these risks. We evaluated the cost-effectiveness of DPYD genotyping prior to capecitabine administration, followed by dose modification for patients with metastatic breast cancer.

AKT is a critical mediator of the phosphoinositide 3-kinase (PI3K) signalling cascade, playing a key role in regulating essential cellular processes. The identification of AKT as one of the most dysregulated pathways in cancer led to the development of multiple classes of inhibitors. Despite numerous inhibitors entering clinical investigation and leading to the FDA approval of Capivasertib, an ATP-competitive AKT inhibitor, in November 2023, AKT modulation through inhibition was characterised by toxicity and poor clinical efficacy. Targeted Protein Degradation (TPD) spearheaded by PROTACs boasted a paradigmatic shift in drug discovery and was demonstrated to be a valid therapeutic alternative to modulate AKT. To date, numerous AKT-targeting PROTACs have been disclosed. The majority of them outperformed the inhibitors in suppressing AKT activity, nurturing higher potency and improved selectivity. Notably, enhanced antiproliferative effects, sustained by more robust and prolonged inactivation of the AKT downstream signalling was observed. This review highlights AKT as a central therapeutic target in oncology and focuses on AKT modulation through a targeted protein degradation approach mainly using PROTACs. The review aims at illustrating all the AKT-targeting PROTACs disclosed in literature to date, a powerful new pharmacological tool that might remarkably expand the scope of AKT-targeted therapies and further elucidate the role of AKT in both normal and cancer-related phenotypes.

Atezolizumab plus bevacizumab (Atezo/Bev) is the standard first-line therapy for unresectable hepatocellular carcinoma (uHCC). In the IMbrave150 trial, bevacizumab-related adverse events (AEs) frequently required dose interruption or discontinuation, raising concerns regarding optimal dosing. The effect of initiating therapy with low-dose bevacizumab remains uncertain.

Background and Objectives: A combination of chemotherapy and immunotherapy may improve cancer treatment outcomes; however, determining which patient groups will benefit from immunotherapy is critical. Triple-negative breast cancer (TNBC) achieves limited benefit from immune checkpoint inhibitors (ICIs) and anti-PD-L1 blockade therapy. Materials and Methods: In this study, PD-L1 expression levels in myeloid-derived cells in the tumor microenvironment were determined in an experimental TNBC model. Results: Compared with tumor cells, granulocytes, monocytes, and macrophages had significantly higher PD-L1 expression. CD206+ tumor-associated macrophages (TAMs) expressed the highest level of PD-L1. PD-L1 positivity in TAMs was also significantly high in the lung, liver, lymph node, and spleen. Despite treatment initiation in late-stage tumorigenesis, the combination of paclitaxel and the anti-PD-L1 monoclonal antibody atezolizumab significantly reduced tumor growth. In addition, lung metastasis burden was reduced with combined treatment compared with chemotherapy or anti-PD-L1 monotherapy alone. Conclusions: As a result, alterations in PD-L1+ myeloid cells and immune infiltration can be associated with atezolizumab and paclitaxel therapy success in triple-negative breast cancer.

Background and objectives: Therapeutic agents for cancer can cause unique pulmonary toxicities and mimic other conditions. The advent of new targeted molecular and immune therapies has changed the landscape of cancer treatment. These adverse events pose diagnostic and therapeutic challenges. This review aims to summarize the clinical presentations, radiographic patterns, and management strategies for noninfectious pulmonary complications associated with cancer therapies. Materials and methods: A literature review was conducted focusing on drug-induced lung injury (DILI), radiation-induced lung injury (RILI), pleural disease, pulmonary vascular complications, and other inflammatory conditions in patients with cancer. The data sources included clinical trials, guideline recommendations, observational studies, and expert consensus addressing incidence, pathophysiology, imaging findings, and treatment approaches. Results: Noninfectious pulmonary sequelae of anti-neoplastic therapies encompass a broad spectrum of etiologies. DILI occurs in up to 30% with variable onset and severity. The patterns can be diverse but include interstitial pneumonitis, organizing pneumonia, and diffuse alveolar damage. RILI is common and influenced by the radiation dose, volume, and concurrent therapies, and it may have both acute and chronic clinical and radiographic presentations. Pleural disease may arise from radiation and other agents, and the determination of etiology can impact management. Pulmonary vascular disease arises from many different etiologies, including therapies such as tyrosine kinase inhibitors and proteosome inhibitors, thromboembolic disease, as well as rare processes, including pulmonary veno-occlusive disease. Other conditions such as transfusion-related lung injury, cryptogenic organizing pneumonia, and interstitial lung abnormalities can also further complicate the diagnosis. Conclusions: Noninfectious pulmonary complications related to cancer therapies are diverse and often indistinguishable from infectious or malignant processes. The integration of clinical history, imaging, and selective invasive testing are needed for a timely diagnosis. Management typically involves withdrawal of the offending agent and corticosteroids, with immunosuppressive therapy reserved for severe or refractory cases. The awareness of these entities and early recognition are critical to optimizing outcomes.

Background/Objectives: This study aimed to investigate the phytochemical composition, antioxidant capacity, and anticancer potential of methanol and ethanol extracts of Lactarius deliciosus (L.) Gray in MCF-7 breast cancer cells, focusing on their effects on energy metabolism and related molecular mechanisms. Methods: In L. deliciosus samples, total antioxidant activity and total phenolic content were determined spectrophotometrically, while individual phenolics were classified by HPLC and volatile aromatic compounds (VOCs) were determined by GC-MS. The anticancer effects of L. deliciosus in MCF-7 breast cancer were determined using RT-qPCR with 46 different genes. Results: Phytochemical profiling via HPLC and GC-MS revealed a rich diversity of bioactive compounds, including significant levels of gallic acid (298.89 µg/g), vanillic acid (191.98 µg/g), and succinic acid (724.73 µg/g). The extracts exhibited robust antioxidant activity and dose-dependent cytotoxicity, reducing cell viability to as low as 5.60% after 72 h. Molecular analysis through Reactome pathway enrichment and expression profiling of 46 genes demonstrated that L. deliciosus drives cancer cells into a metabolic impasse by reversing the Warburg effect. Key findings include the significant downregulation of glycolytic genes like SLC2A1/GLUT1 (-12.34) and HK2 (-1.71), alongside the repression of mitochondrial TCA cycle regulators such as IDH1 (-17.81) and OGDH (-2.54). This metabolic collapse triggered G0/G1 phase cell cycle arrest and induced apoptosis. Conlusions: These results align with international benchmarks for Lactarius species while providing novel insights into the metabolic reprogramming mechanism. The results obtained in this study highlight that L. deliciosus emerges as a promising natural agent for therapeutic strategies targeting cancer bioenergetics.

As a novel form of cell death, the discovery of cuproptosis presents significant opportunities and challenges for the field of cancer therapy. Notably, polyphenolic compounds have attracted considerable research attention for their ability to induce cuproptosis. These natural compounds not only exhibit marked anti-inflammatory and antioxidant properties, but their polyhydroxy structures also enable effective chelation and transport of copper ions. This provides novel insights into cuproptosis-mediated cancer therapy. Therefore, in this review, we systematically outline copper metabolism, the mechanisms of cuproptosis, and its association with cancer, while providing an in-depth discussion of the effects and mechanisms by which polyphenolic compounds act as copper ionophores to inhibit tumor growth and progression through the induction of cuproptosis. This review indicates the promising potential of polyphenolic compounds in the field of cancer therapy and provides a theoretical basis for therapeutic strategies based on cuproptosis.

Curvularins, a class of macrocyclic lactones, have cytotoxic, antimicrobial, and anti-inflammatory properties. Curvularin, a 12-membered macrolactone, was used as a scaffold to design and synthesize structurally modified analogues to investigate structure-activity relationships and improve biological efficacy. Three series of curvularin-based analogues, Cur-5H-OMe, Cur-4P-OMe, and Cur-OMe, were synthesized with the same core structure but different substituent sizes and positions. Nine representative derivatives were evaluated for anti-inflammatory, anticancer, antibacterial, and antifungal activities. In LPS-stimulated RAW 264.7 macrophages, most compounds inhibited nitric oxide (NO) production in a concentration-dependent manner but exhibited cytotoxicity at high concentrations. Cytotoxicity assays against HaCaT cells and human cancer cell lines (HCT116, HeLa, and A375) revealed limited selectivity toward cancer cells. Antimicrobial evaluation indicated selective activity against the Gram-positive bacteria, Staphylococcus aureus. Compound 23 exhibited superior antibacterial potency compared with kanamycin and notable antifungal activity against Candida albicans. This study provides a versatile synthetic platform and identifies key structural features of curvularin derivatives, demonstrating their potential as anti-inflammatory and antimicrobial lead compounds.

According to the World Health Organization, antibiotic research remains insufficient, emphasizing the urgent need for new active molecules, particularly against resistant bacteria. Based on known antibacterial scaffolds, new fluoroquinolone derivatives have been synthesized by our research group, including compound 7a, a difluoroboranyl-fluoroquinolone that previously demonstrated activity against sensitive strains.