Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the immunohistochemical images shown in Fig. 1A on p. 1377, the 'DNMT3A' and 'DNMT3B' images for the 'BN' row of data contained an overlapping section, such that date which were intended to show the results from differently performed experiments had apparently been derived from the same original source. In addition, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that the same data had been included for the Petri dish images in Fig. 3B on p. 1382 for the DMSO experiments with the T24 and EJ cell lines, albeit the EJ image had been rotated through 90°. The authors were contacted by the Editorial Office to offer an explanation for this apparent duplication of data within these figures; however, up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 35: 1375‑1384, 2016; DOI: 10.3892/or.2015.4492].

A novel 5 mg mini-tablet formulation of mercaptopurine (6-MP) was developed to provide flexible and accurate doses to treat children with acute lymphoblastic leukemia. We conducted two open-label, randomized, single-dose, four-period, two-sequence, full-replicate, crossover trials to characterize the pharmacokinetics and relative bioavailability of the novel 6-MP mini-tablet (N) compared to the reference 6-MP tablet (R) under both fasted and fed conditions. The 6-MP plasma concentrations were measured using ultra performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS). The Cmax, AUC0-t, and AUC0-inf were used to evaluate the relative bioavailability. The results showed that the 6-MP mini-tablet was bioequivalent to the reference formulation under fasting condition. Under the fasted condition, the geometric least-squares mean ratios (GLSMR) (90% CI) of Cmax, AUC0-t, and AUC0-inf of N over R were 91.71% (81.31%-103.44%), 97.53% (92.57%-102.76%), and 97.91% (93.17%-102.90%), respectively. The mean CL/F (238.4 vs 219.3 L/h), the mean Vd/F (523.4 vs 451.8 L), the median Tmax (1.50 vs 1.25 h), and the mean t1/2 (1.55 vs 1.44 h) of N and R showed similarity. Under fed condition, the GLSMR (90% CI) of Cmax, AUC0-t, and AUC0-inf of N over R were 68.16% (59.62%-77.93%), 86.22% (81.37%-91.37%), and 86.59% (81.88%-91.57%), respectively. Furthermore, a high-fat diet increased both CL/F and Vd/F of 6-MP and decreased exposure of 6-MP, with all changes exceeding two-fold. Both products exhibited a favorable safety profile without any SAE being observed. These results supported the marketing of 6-MP mini-tablets.

Brazilin (BRZ), a major bioactive constituent of Caesalpinia sappan, exhibits promising anticancer activity but suffers from extremely poor aqueous solubility, limiting its oral bioavailability and therapeutic efficacy. Drug solubility is a critical determinant of absorption and therapeutic efficacy, so strategies to enhance the solubility of BRZ are essential. Amorphous solid dispersions (ASDs) have been widely employed to enhance the solubility and dissolution behavior of poorly soluble compounds. This study aimed to develop and characterize ASDs of BRZ using polyvinylpyrrolidone (PVP) as a polymer carrier, to investigate molecular interactions through in silico docking, and to evaluate their physicochemical properties, dissolution behavior, physical stability, and antiproliferative activity.

ADP-ribosyltransferases (ARTs) regulate key processes in cancer, including DNA repair, transcription, immune responses, and treatment resistance. The clostridial toxin-like ADP-ribosyltransferase (ARTC) family and the diphtheria toxin-like ADP-ribosyltransferase (ARTD) family play a crucial role in genomic stability by modification of proteins either with mono(ADP-ribosyl)ation (MARylation) or poly(ADP-ribosyl)ation (PARylation). These ARTs are promising therapeutic targets and could serve as biomarkers in cancer management. This review explores the roles of these enzymes and current knowledge on specific inhibitors. A literature search was conducted in PubMed and Google Scholar to identify studies published between 1992 and 2025 on ADP-ribosyltransferases and their roles in cancer. Among ARTC family, ART1 and ART3 modulate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, influencing angiogenesis, tumor growth, and immune evasion via cluster of differentiation 8+ (CD8+) T-cell apoptosis. Within the ARTD family, poly(ADP-ribose)polymerase (PARP)1 and PARP2 are activated by DNA single-strand breaks and are clinically validated targets in cancers with homologous recombination deficiency, such as breast cancer susceptibility genes 1/2 (BRCA1/2)-mutated breast cancer. Their inhibition exemplifies synthetic lethality and has shown clinical efficacy. Four PARP inhibitors, olaparib, niraparib, rucaparib, are approved by the Food and Drug Administration (FDA) approved. Despite these advances, selective inhibitors for ARTs remain underexplored. Ongoing research focuses on overcoming PARP inhibitor resistance, improving biomarker-driven patient selection, and expanding therapeutic strategies that target ART-related pathways.

Combined chemotherapy and photothermal therapy (PTT) represents a promising approach for enhancing cancer treatment efficacy. This study aimed to develop arsenic trioxide (ATO) and poly(cyclopentadithiophene-alt-benzothiadiazole) (PCPDTBT)-loaded nanoparticles (ATO/PCPDTBT@NPs) to evaluate their synergistic efficacy in inhibiting lung cancer growth and metastasis.

Drug resistance is the major determinant of chemotherapy failure, leading to relapse and tumor progression, demonstrating the urgent need for novel antineoplastic drugs. This study aimed to evaluate the anticancer potential of two novel pyrazole derivatives, P3C.1 and P3C.2, and to elucidate their mechanism of action in cancer cells.

MicroRNAs (miRNAs) are small, non-coding RNAs that play a key role in the development of chemoresistance in various cancer types, including colorectal cancer (CRC). In this study, we aimed to study the underlying mechanisms of miRNA in chemotherapy-resistant CRC.

Prostate cancer cells often develop mechanisms to evade conventional therapies. Nanomedicine offers the potential for targeted drug delivery, improved tumor accumulation, and reduced systemic toxicity. This study biosynthesizes silver nanoparticles (NPP/AgONPs) functionalized with propolis, evaluates their antibacterial efficacy against uropathogenic strains of Escherichia coli (E. coli), and assesses their cytotoxic effect on cancer cell proliferation using the PC-3, human prostate epithelial cell line.

Glioblastoma (GBM) remains the most prevalent and aggressive primary central nervous system (CNS) malignancy; however, the clinical efficacy of the preferred chemotherapeutic agent, Temozolomide (TMZ), is severely compromised by innate and acquired resistance. Sphingolipid metabolism acts as a pivotal regulator of GBM cell fate, and the imbalance of the "sphingolipid rheostat" is intimately linked to TMZ resistance. This provides potential targets for developing novel prognostic models to inform stratified treatment risk strategies, while offering a promising entry point for TMZ chemosensitization and stratified drug combinations.

The therapeutic landscape for deficient mismatch repair (dMMR) colorectal cancer (CRC) has been fundamentally transformed by the introduction of immune checkpoint inhibitors (ICIs). Yet, a significant fraction of patients exhibits primary or acquired resistance, underscoring a critical unmet need to decode the heterogeneity of tumor-infiltrating CD8+T cells. Identifying the effector subsets that truly drive tumor control will be essential for refining patient stratification and optimizing therapeutic interventions.

Nimotuzumab, a humanized immunoglobulin G1 monoclonal antibody, is mainly used in combination with radiotherapy for the treatment of stage III/IV nasopharyngeal carcinoma (NPC) or locally advanced head and neck squamous-cell carcinoma (HNSCC) with positive epidermal growth factor receptor (EGFR) expression. Although the drug has a favorable safety profile, it is associated with various adverse reactions, among which hypotension is relatively uncommon. Clinically, hypotension caused by nimotuzumab mainly manifests as mild blood pressure (BP) reduction, which can be relieved via rest. This case reports a 65-year-old male patient with advanced NPC who developed severe persistent hypotension after receiving radiotherapy combined with 5 cycles of nimotuzumab treatment. After excluding related factors such as cardiac function, endocrine function, thyroid function, inflammatory factors and other drugs, the adverse reaction was considered to be closely associated with nimotuzumab. After discontinuing the drug and giving continuous norepinephrine to increase BP, the patient's BP returned to stable. This case suggests that although nimotuzumab-related hypotension is mostly mild and reversible, BP monitoring should still be strengthened to maintain vigilance against severe hypotension and intervene promptly in clinical practice.

Long-term immunosuppression following organ transplantation results in an elevated risk of malignancies in recipients, which constitutes a major factor limiting their long-term survival. Therefore, the development of immunosuppressant with anti-tumor efficacy holds critical significance. Icaritin (ICT), a clinically employed antitumor drug, enhances anti tumor immunity by reshaping the tumor immune microenvironment. Moreover, recent evidence highlights its immunomodulatory role in mitigating multiple autoimmune diseases. However, whether ICT can attenuate the allograft rejection remains poorly characterized.

Colorectal cancer (CRC) remains a major global health challenge, with current therapeutic options often limited by drug resistance and adverse effects. Small molecules provide distinct advantages, including oral bioavailability, cost-effectiveness, and the ability to target intracellular pathways critical for tumor progression. In this study, we designed and synthesized a new series of pyrazolone derivatives with varied substitution patterns using microwave-assisted methods and evaluated their antiproliferative activity against CRC cell lines (HCT-116 and WiDr). Among these, PL-13 emerged as a potent and selective candidate, exhibiting strong cytotoxicity toward cancer cells while sparing noncancerous CRL-1459 colon cells. Functional assays, including colony formation and wound healing, confirmed its ability to inhibit cell proliferation and migration. Western blot analyses demonstrated that PL-13 induces apoptosis via the intrinsic mitochondrial pathway, as evidenced by increased levels of cleaved caspase-9 and PARP, and modulates LC3A/B expression, suggesting involvement of autophagy. Kinome profiling revealed selective binding of PL-13 to FLT3, which was validated by an IC50 value of 8.2 μM. Molecular docking further supported these findings, showing favorable binding energy (-7.98 kcal/mol) compared to regorafenib (-7.13 kcal/mol). Collectively, these results highlight PL-13 as a promising lead compound for further optimization toward CRC therapy.

Vascular tumours and malformations encompass infantile hemangiomas (IHs) and genetically driven vascular malformations with distinct natural histories and therapeutic vulnerabilities. The discovery that the non-selective beta-blocker propranolol induces rapid regression of proliferating IHs established the first widely adopted systemic pharmacologic therapy in vascular anomaly care and provided a clinical proof-of-concept that targeting lesion-specific endothelial biology can alter disease course. In parallel, recurrent somatic variants affecting PI3K/AKT/mTOR (e.g., PIK3CA, TEK/TIE2, AKT1) and RAS/MAPK (e.g., KRAS, NRAS) signalling have reframed many malformations as mosaic disorders amenable to targeted inhibition with agents such as sirolimus, alpelisib, AKT inhibitors and MEK inhibitors. This review synthesizes translational mechanisms, clinical evidence and safety considerations for beta-blockers and emerging targeted therapies, emphasizing lesion phenotype, timing of intervention and molecular stratification as determinants of response. We highlight current limitations, including toxicity, durability and pathway escape, and outline future directions for precision therapy and genotype-guided trial design in vascular anomalies.

Drug resistance, also known as chemoresistance, is a known impediment in fighting cancers. Pak1 (p21-activated kinase), a serine/threonine kinase, is a known oncogene implicated in tumor progression and associated with poor prognosis in cancer patients. Pak1 has been reported to be mechanistically contributing to drug resistance to tamoxifen and gemcitabine. Using an integrative approach, the present study investigated Pak1 and its precise role in conferring chemoresistance alongside other known kinases. Study identified 25 additional kinases contributing to resistance to 12 commonly used drugs in clinics for the treatment of breast, head and neck, and pancreatic cancers. The study analysis revealed that mutated Pak1 and more than one kinase were likely to be involved in drug resistance in patients associated with poor prognosis. The study concluded that the detection of altered kinases in resistant tumors is imperative, and a combination of kinase inhibitors could be useful for treatment rather than single agents to improve treatment outcomes.

Triple-negative breast cancer (TNBC) remains a therapeutic outlier, with limited targeted options and frequent relapse despite chemotherapy. While platinum therapy can benefit some TNBC cases, including BRCA1/2-mutant tumors, toxicity and limited tumor-selective exposure often restrict its impact. To address these barriers, we applied a lipid-metallodrug prodrug approach and synthesized an oxaliplatin-oleic acid (OXA-OA) conjugate that coupled OXA's cytotoxicity with OA-associated anticancer activity. The prodrug was encapsulated into genipin-crosslinked albumin nanoparticles (OXA-OA Alb NPs) to improve tumor targeting, yielding a uniform size of 140.52 ± 4.35 nm, a PDI of 0.25 ± 0.05, and an encapsulation efficiency of 84.55 ± 4.49%. Spectrometric analysis confirmed successful OXA-OA conjugation. The nanoparticles demonstrated enhanced cellular uptake and tumor targeting. In vitro, OXA-OA Alb NPs reduced the IC50 to 0.19 ± 0.36 µg/mL (4T1) and 0.20 ± 0.16 µg/mL (MDA-MB-231). This corresponded to 25 to 30-fold higher cytotoxicity than free OXA and > 50-fold than OA. Furthermore, apoptosis indices reached 1.47 (4T1) and 1.42 (MDA-MB-231), which were 4.19- and 4.50-fold higher than OA and 2.43- and 2.53-fold higher than OXA. In vivo, OXA-OA Alb NPs achieved ~ 90% tumor inhibition in a TNBC mouse model, with minimal systemic toxicity, stable liver and kidney function, and reduced organ damage compared with other treatment groups. These findings suggest that OXA-OA Alb NPs offer a promising and safer approach for TNBC, with potential for further exploration in preventing metastasis and recurrence.

To mitigate the severe adverse effects associated with the systemic administration of doxorubicin (DOX), this study developed a dissolving microneedles (MN) patch loaded with doxorubicin hydrochloride (DOX-MN) for the local treatment of breast cancer. It specifically investigated the influence and underlying mechanisms of drug loading and application force on drug bioavailability. DOX-MN with intact structure and drug enrichment at the needle tips were successfully fabricated using a centrifugal micro-molding technique. Characterization confirmed the excellent mechanical strength and skin insertion capability of the MN, which dissolved rapidly and released the drug within 30 min. In vivo pharmacokinetic studies identified drug loading and application force as critical determinants of bioavailability. A high drug loading potentially created a local supersaturated state, enhancing drug penetration and achieving a relative bioavailability of 65.25%. Increasing the application force to 25 N effectively minimized drug residue on the skin surface, improving bioavailability by approximately 1.5-fold. In a 4T1 tumor-bearing mouse model, DOX-MN administration facilitated efficient drug enrichment and sustained retention at the tumor site, yielding a tumor inhibition rate (90.61%) comparable to intravenous injection. Safety assessments indicated that using a dedicated applicator significantly reduced skin irritation. This study demonstrates that optimizing drug loading and application force enables efficient local DOX delivery via MN, ensuring potent antitumor efficacy while minimizing systemic toxicity, thereby presenting a promising novel strategy for breast cancer therapy.

We describe a case of febrile neutropenia in a patient with metastatic non-small cell lung cancer, occurring after 36 cycles of nivolumab therapy. A bone marrow aspirate was performed which showed myeloid maturation arrest without a clear alternative cause, supporting an immune-mediated mechanism. The patient responded well to broad-spectrum antibiotics and granulocyte colony-stimulating factor (G-CSF), with successful rechallenge until other immune-related toxicities led to discontinuation. While uncommon, haematological immune-related adverse events are potentially life-threatening, with neutropenia reported in <1% of patients treated with immune checkpoint inhibitors. This case demonstrates three important points: (1) neutropenia may occur even late in the course of treatment with immunotherapy, highlighting the persistent need for vigilance; (2) bone marrow biopsy and the careful review of medications are essential to differentiate immune-mediated from chemotherapy or other drug-related cytopenias; and (3) management requires urgent recognition, antimicrobial cover, and G-CSF, and caution in the consideration of rechallenge.

Increasing survival rates following cancer diagnoses, combined with demographic aging, have resulted in a growing population of long-term survivors. Many of these individuals face persistent and late-onset effects of oncological treatments. This article examines the most common sequelae associated with traditional treatment approaches, presents emerging evidence on innovative therapies, and explores their impact on patients' quality of life.

Accurate prediction of peptide-protein interactions (PepPI) is crucial for advancing peptide-based anticancer drug design. In this study, we introduce ProVenTL, a computer-aided molecular design framework that leverages transfer learning and protein language model embeddings to enhance PepPI prediction accuracy and interpretability. Two complementary strategies were explored: (i) fine-tuning a CAMP model pretrained on large-scale PepPI data from the Protein Data Bank (PDB) using a curated dataset of Calloselasma rhodostoma venom peptides and cancer-related proteins, and (ii) integrating ProtT5 embeddings with stacked autoencoder-deep neural networks (SAE-DNN) and TabNet classifiers. Models were comprehensively benchmarked against baseline configurations and representative deep-learning approaches using standard classification metrics, while biological relevance was evaluated through functional enrichment and pathway analysis of top-ranked predictions. Compared with baseline configurations and conventional deep-learning approaches, the ProtT5-based SAE-DNN model achieved the best performance (accuracy = 0.78; ROC-AUC = 0.86), demonstrating improved generalization capability on a small, domain-specific venom peptide dataset. The model identified key targets such as TRBC2, CD274, HIF1AN, PCSK9, and PLAU, which are associated with pathways involved in immune suppression, hypoxia regulation, lipid metabolism, and metastasis. This study highlights the utility of transfer learning and protein language models for PepPI prediction in data-limited scenarios and establishes a computational framework for prioritizing snake-venom-derived peptides for anticancer drug discovery and future experimental validation.