Monensin, a polyether ionophore widely used in veterinary medicine, has recently emerged as a multimodal anticancer candidate. This review provides a comprehensive overview of preclinical studies showing that monensin exerts selective cytotoxic and anti-progression effects across a wide range of malignancies. Its activity spans breast cancer to leukemia, reflecting both versatility and significant therapeutic potential. In breast cancer, monensin reduces proliferation, induces apoptosis, and enhances chemosensitivity, suggesting a role in combination therapies. In prostate cancer, it disrupts androgen receptor signaling, induces oxidative stress, and triggers mitochondria-dependent apoptosis. In pancreatic cancer, it suppresses EGFR signaling and promotes programmed cell death, while in ovarian and cervical cancers, it inhibits proliferation, migration, and invasion by modulating EGFR and MEK/ERK pathways and enhancing SUMOylation. In renal carcinoma, monensin induces cell-cycle arrest, autophagy, and apoptosis, whereas in bladder and squamous cell carcinoma, it interferes with EGFR-related signaling and lectin-mediated interactions. It selectively kills liver cancer cells through intracellular Na⁺ overload and mitochondrial damage, and in thyroid cancer, it disrupts cellular respiration and AMPK/mTOR signaling. In glioblastoma, it exhibits both anti-tumor and anti-angiogenic effects, while in hematologic malignancies such as leukemia and lymphoma, it induces apoptosis, cell-cycle arrest, and glycosylation alterations. Collectively, these findings highlight monensin as a highly promising, broad-spectrum anticancer candidate. Its multifaceted mechanisms of action and consistent efficacy across diverse tumor types provide a compelling rationale for continued preclinical evaluation and potential clinical translation. These insights position monensin as an innovative therapeutic avenue, offering new hope for the development of versatile and effective cancer treatments.

Conventional photosensitizers (PSs) are hindered by aggregation-caused quenching, limited tissue-penetration depth and off-target toxicity, which restricts their clinical translation for photodynamic therapy (PDT). To tackle these bottlenecks, we constructed an all-in-one nanotheranostic system named F127@546, where a donor-acceptor-type fluorophore (IR-546) with twisted intramolecular charge-transfer (TICT) characteristics is encapsulated within the amphiphilic polymer Pluronic F127. This rational design not only substantially improves biocompatibility but also induces a prominent emission red shift from 605 nm to 900 nm, with an emission tail extending above 1000 nm to realize high-resolution deep-tissue NIR-II imaging. Beyond its NIR-II imaging capability, F127@546 acts as an effective dual-mode photosensitizer upon 660 nm laser irradiation to concurrently produce type-I and type-II reactive oxygen species (ROS). The generated ROS dissipates mitochondrial membrane potential and further initiates melanoma cell apoptosis. In vivo experiments were performed via intratumoral injection of F127@546. We verified that its photodynamic therapy exerted a remarkable inhibitory effect on tumors, accompanied by negligible systemic toxicity. This study provides a generalizable blueprint for fabricating multifunctional nanoplatforms that combine deep tissue imaging and synergistic photodynamic therapy, advancing the development of precision-oriented anti-tumor treatment.

Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown limited efficacy in gastric cancer, primarily due to the rarity of inherent homologous recombination (HR) deficiency. The nuclear Arp2/3 complex was recently implicated in DNA double-strand break repair via HR. Here, we investigate whether pharmacological inhibition of Arp2/3 can induce a functional HR-deficient state to synergize with PARPi in gastric cancer cells.

Glioblastoma (GBM) frequently develops resistance to temozolomide (TMZ), limiting the effectiveness of standard therapy. Histone deacetylase (HDAC) inhibitors have emerged as potential chemosensitizers; however, the comparative performance of these inhibitors and the associated mechanistic impact remain incompletely characterized.

Cancer neuroscience has emerged as a field that explores the bidirectional interactions between tumors and the nervous system. From this perspective, we review the pharmacological and neurobiological effects of kinase inhibitors, which are widely used as anticancer therapeutics. Certain kinase inhibitors not only exert potent antitumor activity but also modulate neural function as a consequence of kinase inhibition. Representative examples include small molecules and therapeutic antibodies targeting the tropomyosin receptor kinase (Trk), rearranged during transfection (RET), vascular endothelial growth factor/ vascular endothelial growth factor receptor (VEGF/VEGFR), epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) signaling pathways. These agents influence the nervous system through molecular mechanisms, examples of which include TrkA-mediated pain perception and growth differentiation factor 15/RET signaling-dependent appetite regulation. Elucidating these mechanistic intersections between oncogenic and neural signaling can broaden our understanding of tumor-nerve crosstalk.

A common cause of multidrug-resistant (MDR) cancer is imbalanced redox signaling, which reduces the effectiveness of chemotherapy and promotes regrowth of cancer cells. Amplification of thioredoxin reductase (TrxR) and activation of the Keap1-Nrf2-FOXO3 pathway may contribute to enhanced drug efflux, strengthens antioxidant defenses, and resistance to oxidative stress-induced apoptosis in certain tumors. Redox-based drug repurposing offers a promising strategy to overcome MDR by targeting these shortcomings. Repurposing drugs including metformin, auranofin, brusatol, and natural polyphenols increase reactive oxygen species (ROS) and make MDR cells more sensitive to chemotherapy via modulation and inhibiting Nrf2 or TrxR. Nanotechnology advancements and combination of repurposed drugs with anticancer drugs, ferroptosis inducers may improve tumor selectivity while lowering systemic toxicity. Preclinical experiments show effectiveness by suppressing antioxidant pathways, inhibiting efflux pump function, and delivering drugs in a redox-responsive manner. Next-generation tumor-selective delivery systems, adaptive clinical trial designs, and biomarker-driven patient classification based on TrxR expression or Keap1/Nrf2 mutations are the main areas of focus. Translation into clinical practice could be accelerated by combining specific redox profiling, nanocarrier technologies, and pharmacokinetics. For MDR cancer, redox-targeted drug repurposing is an effective, precision-based strategy for recovering chemosensitivity and enhancing treatment outcomes.

Acute myeloid leukemia (AML) remains a highly aggressive hematological malignancy with frequent relapse and limited therapeutic durability. Although venetoclax has provided an important therapeutic option for AML, suboptimal response and treatment resistance continue to restrict its clinical benefit. Here, we developed a venetoclax-loaded lipid nanomedicine, Vene-lipo, to enhance anti-leukemic efficacy. Vene-lipo displayed uniform nanoscale morphology, favorable colloidal stability, and good preliminary biosafety. Compared with free venetoclax, Vene-lipo more effectively suppressed AML cell growth and promoted ROS-associated DNA damage and apoptosis. In vivo, Vene-lipo reduced leukemic burden, alleviated leukemia-associated organ involvement, improved hematological abnormalities, and prolonged survival. These findings demonstrate that lipid nanomedicine-based delivery can potentiate the therapeutic activity of venetoclax and provide a promising strategy for AML treatment.

To assess the protective effects of live combined bifidobacterium, lactobacillus, enterococcus, and glutamine on diarrhea associated with chemotherapy and inflammatory markers in colorectal cancer patients (CCP). A retrospective analysis was conducted on the clinical data of patients with colorectal cancer who received chemotherapy at the People's Hospital of Pailin County, Chongqing from December 2022 to December 2024. There were 59 cases in the control group and 59 cases in the study group. The control group received treatment with triple live bifidobacterium, while the study group received combined treatment with glutamine in addition to the treatment of the control group. We compared levels of inflammatory markers, intestinal barrier functions, immune responses, and diarrhea incidence during chemotherapy. No significant pre-chemotherapy differences were noted in inflammatory or intestinal barrier markers (P > 0.05). Throughout the course of treatment, we observed a reduction in inflammatory markers in both groups (P < 0.05), with the experimental group showing more significant declines. Intestinal barrier functions degraded over time in both groups, with more significant reductions in the study group (P < 0.05). The therapy combining significantly mitigates inflammation, bolsters intestinal and immune functions, and alleviates diarrhea in CCP. Clinical Registration: The authors have nothing to report.

A subset of cancer patients receiving monoclonal antibody PD-1/PD-L1 inhibitors may develop immune checkpoint inhibitor (ICI)-related neurological complications, such as ICI-related myasthenia gravis(MG)-myositis overlap syndrome and ICI-related myocarditis. Standard management typically involves intravenous immunoglobulin (IVIG), plasma exchange (PE), and high-dose corticosteroids. The use of efgartigimod, a neonatal Fc receptor blocker, for the treatment of ICI-related MG-myositis overlap syndrome remains investigational, with only four relevant cases all representing overlap syndromes (MG with myositis, with or without myocarditis) - reported to date.

Immune checkpoint inhibitors (ICIs) can induce a broad spectrum of immune-related adverse events (irAEs), including rare fibroinflammatory autoimmune manifestations. IgG4-related disease (IgG4-RD) has only exceptionally been described following dual ICI therapy.

Immune checkpoint inhibitors (ICIs) activate antitumor immunity by targeting immune checkpoint molecules such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death receptor 1 (PD-1), and programmed death-ligand 1 (PD-L1). They have emerged as a key therapeutic modality for multiple malignancies. Nevertheless, excessive immune activation may trigger a spectrum of immune-related adverse events (irAEs). Though uncommon, uveitis is a sight-threatening irAEs that can result in permanent visual loss. The risk and prognostic outcomes of ICIs-associated uveitis remain poorly defined to date. Therefore, we performed this meta-analysis to systematically assess the correlation of ICIs therapy with uveitis risk and prognosis, with the goal of providing evidence-based recommendations for clinical identification and management of this ocular complication.

4-[4-(Bis(2-(nitrooxy)ethyl)amino)phenyl]butanoic acid (NPB), a phenylbutyrate-derived nitric oxide (NO) donor, has been developed as a potential anticancer agent for pancreatic cancer. In the present study, we investigated the cytotoxic effects of NPB under cellular stress conditions and examined its effects on autophagy-related pathways and hypoxia-inducible factor-1α (HIF-1α) signaling. NPB-induced cell death was enhanced under nutrient-deprived conditions in PANC-1 cells. In addition, NPB induced greater cell death under hypoxic conditions than under normoxic conditions in PANC-1 cells, whereas in BxPC-3 cells, NPB-induced cell death was slightly but significantly lower under hypoxic conditions than under normoxic conditions. Using GFP-LC3-RFP-LC3ΔG reporter cells, NPB suppressed starvation-induced autophagic flux. In pancreatic cancer cells, NPB decreased DAPGreen fluorescence, an indicator of autophagy-related vesicular activity, and increased propidium iodide-positive cells under hypoxic conditions. Western blot analysis showed that NPB induced the accumulation of p62 and LC3 under both normoxic and hypoxic conditions. Under hypoxic conditions, NPB also reduced HIF-1α expression. Under cobalt chloride (CoCl2)-induced HIF-1α-accumulating conditions, NPB and the NO donor NONOate suppressed HIF-1α expression, whereas OH-PB, a non-NO-releasing analog, showed little effect. Furthermore, the proteasome inhibitor MG132 restored HIF-1α accumulation in NPB-treated cells. Time-course analysis under CoCl2-treated conditions showed that NPB reduced HIF-1α expression concomitantly with p62 accumulation. These findings suggest that NPB induces pancreatic cancer cell death, particularly under nutrient-deprived and hypoxic conditions, accompanied by impairment of autophagy-related pathways and NO-dependent, proteasome-associated reduction of HIF-1α.

The optimal choice between sedating histamine H1 antagonists (sAHs) and non-sedating histamine H1 antagonists (nsAHs) for preventing infusion-related reactions (IRRs) during daratumumab subcutaneous (DARA-SC) therapy remains unclear. Here, we aimed to compare the efficacy and safety of nsAH and sAH as premedication for DARA-SC therapy. Patients with multiple myeloma or light-chain amyloidosis who received DARA-SC therapy at eight hospitals were enrolled in this prospective, multicenter, observational study. Patients were categorized into nsAH and sAH groups based on their premedication. IRRs and drowsiness were assessed using patient-reported questionnaires, including the Stanford Sleepiness Scale (SSS) and the Japanese Epworth Sleepiness Scale (JESS), at baseline, post-administration (Q2), and before bedtime (Q3). Overall, 104 patients (nsAH, n = 49; sAH, n = 55) were analyzed. No significant differences were observed in the IRR incidence between the nsAH and sAH groups at Q2 (8.2 vs. 9.1%) or Q3 (13 vs. 17%). Conversely, the incidence of new-onset drowsiness at Q2 was significantly lower in the nsAH group (13%) than in the sAH group (32%, p < 0.05). Additionally, the increase in SSS from baseline to Q2 was significantly lower in the nsAH group than in the sAH group (p < 0.05). No significant differences were observed in JESS scores. Thus, nsAH was associated with reduced early post-administration drowsiness and there were no statistically significant differences in IRR preventive effects compared to that for sAH, suggesting that nsAH may reduce sedation without a significant increase in the incidence of IRRs; however, these hypothesis-generating findings warrant verification through future prospective comparative trials.

Given the limited Japanese real-world evidence, this study aimed to evaluate the survival and safety of adjuvant nivolumab after neoadjuvant chemotherapy in patients with an incomplete pathological response to esophageal squamous cell carcinoma (ESCC).

Curcumin is a naturally occurring bioactive compound with well-characterized anti-inflammatory and antitumor properties; however, its clinical utility is limited by poor bioavailability and chemical instability. To overcome these limitations, various curcumin analogs have been developed. In this study, we investigated the antitumor and antimetastatic effects of 3,5-bis(2'-ethoxybenzylidene)-piperidine-4-one (E145), a monocarbonyl curcumin analog, with a particular focus on its ability to inhibit nuclear factor-kappaB (NF-κB) signaling in breast cancer cells. We first evaluated the effects of E145 on cell proliferation in murine 4T1 and human MDA-MB-231 breast cancer cell lines. E145 inhibited cell proliferation in a dose-dependent manner and suppressed phosphorylation of the NF-κB p65 subunit. Furthermore, E145 blocked tumor necrosis factor alpha-induced NF-κB activation by inhibiting both p65 phosphorylation and nuclear translocation. Consistently, E145 reduced the expression of NF-κB-regulated pro-tumorigenic factors, including vascular endothelial growth factor, matrix metalloproteinase-9, interleukin-1β (IL-1β), and IL-6. Functional assays demonstrated that E145 markedly suppressed the migration and invasion of breast cancer cells in vitro. In addition, experimental lung metastasis assays revealed that E145 treatment significantly reduced metastatic colonization of 4T1 cells in vivo. Collectively, these findings indicate that E145 exerts potent antimetastatic effects by inhibiting cell-intrinsic NF-κB activation and downstream inflammatory mediators. These results suggest that E145 is a promising therapeutic candidate for targeting NF-κB-driven breast cancer progression and metastasis.

Genetic profiling of a new HPV-negative cervical cancer model identified pathogenic variants in genes implicated in oncogenic signaling, cell cycle regulation, and DNA damage repair pathways, including homologous recombination, non-homologous end-joining, and mismatch repair. Deficiencies in BRCA2, RAD51 and MLH1 were among these actionable targets. The newly described cervical cancer model revealed sensitivity towards the PARP inhibitor olaparib, which was further augmented upon combination with platinum-based chemotherapeutics. In contrast, BRCA1/2-proficient cervical cancer cells exhibited greater resistance to these strategies. This study highlights the potential of in-depth genetic analysis to identify genetic susceptibilities to guide personalized medicine approaches.

Pediatric osteosarcoma is a rare and aggressive malignancy with limited treatment options in cases of progression or metastasis. Regorafenib is an oral multikinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and other kinases, currently approved in Japan for certain gastrointestinal cancers. Its clinical use in osteosarcoma, especially in pediatric patients, has not been well established.

Flavones are naturally occurring compounds with a wide range of biological activities and therefore they represent a privileged scaffold in medicinal chemistry. We recently reported the systematic synthesis of 3-styrylflavones possessing variously hydroxylated D-ring moieties, which indicated significant antiproliferative activity. To determine how the bioisosteric replacement, such as the replacement of a hydroxyl group by an amino/nitro group, influences antiproliferative activity, we designed and synthesized a series of 3-styrylflavones possessing variously nitrogenated D-ring moieties.

Matrix metalloproteinases (MMPs) are important enzymes in extracellular matrix degradation. Several cancer types overexpress MMPs, indicating that MMP inhibition may be a viable approach to induce antitumor activity. To explore this, we designed UTX-121, a molecule in which the sulfonamide group of celecoxib is replaced with a methyl ester group. From this structure, a range of UTX-121 derivatives were developed in which the tolyl moiety was modified. The MMP inhibitory effects of these derivatives were then examined.

Dihydroaustrasulfone alcohol (DA), a synthetic precursor of austrasulfone derived from the soft coral Cladiella australis, has demonstrated cytotoxic activity against various cancer types. However, its antitumor effects and underlying mechanisms in human leukemia cells remain unknown. This study aimed to investigate the anticancer effects of DA in leukemia cell models and to elucidate its mechanisms of action.