Gynecological cancers represent one of the leading causes of death in women and pose a critical global health challenge. While surgery and chemotherapy remain the first-line therapies for gynecological cancers, the persistently high morbidity and mortality rates have driven the urgent exploration of novel theranostic strategies. In recent years, polymer nanoparticles (PNPs) have gained increasing attention in the diagnosis and treatment of cancer due to their superior targeting ability and delivery efficiency. This review provides an overview of PNPs and their role in tumor diagnosis and treatment, with a strategic focus on their utility in gynecological cancers. It covers drug delivery, imaging, combination therapy, and theranostic integration in gynecological cancers, and summarizes the composition, principles and characteristics of diverse polymers and their cargoes. Furthermore, this work highlights innovative applications of PNPs in gynecological cancers management, spanning chemotherapy, immunotherapy, PARPi therapy, phototherapy and other therapies. Despite promising preclinical advancements in PNPs, formidable challenges persist in their clinical translation. This review serves as a comprehensive resource for researchers and clinicians aiming to optimize gynecological cancers theranostics as well as accelerate the development and clinical translation of PNPs.

The hypoxic tumor microenvironment (TME) significantly impacts the effectiveness of various therapies on breast cancer. Conventional chemotherapeutic agents are unable to target hypoxic tumor tissue specifically, leading to reduced treatment efficacy and severe systemic toxicity. In order to improve drug targeting ability, we developed a bioactive biomotors system (MDPP@Bif) for chemoimmunotherapy against breast cancer. Utilizing the self-driving properties of the anaerobic Bifidobacterium infantis (B. infantis, Bif), both doxorubicin (DOX) and anti-programmed cell death protein ligand-1 (αPD-L1) antibody can be delivered simultaneously to tumor tissues to exert an anti-tumor effect on breast cancer.

Cancer represents a complex group of diseases characterized by abnormal cell proliferation, invasion, and metastasis. These features pose significant challenges to conventional therapeutic approaches, necessitating the development of more targeted and effective treatment strategies.

To elucidate the potential targets and mechanisms of Brucea javanica in the treatment of oral squamous cell carcinoma (OSCC) through network pharmacology and molecular docking, supported by clinical data and in vitro experiments.

To investigate the impact of tamoxifen dose, CYP2D6 inhibitors, CYP2D6*4 genotype, and non-genetic parameters on the outcomes of tamoxifen treated female breast cancer patients.

Metastatic tumor cells that escape from immune surveillance are a dilemma in cancer treatment, and thus developing selective targeting agents to treat metastatic tumor and reinstate immune perception is imperative for clinical applications. Herein, a multifunctional nanoplatform of supramolecular assembled nanoparticles (SANs) comprising a core structure of metal ion (Fe3+) and organic ligands including tannic acid (TA), and zoledronic acid (Zol) was developed. The FTZ SANs was further decorated with fucoidan (Fu), a P-selectin ligand, which greatly enhanced specific binding affinity of FTZ@Fu SANs towards metastatic tumor cells and suppressed tumor aggressiveness. The Fe-TA-Zol coordination network constructed through competitive ligand substitution facilitated the releases of Zol in response to the acidic tumor microenvironment (TME), which also benefited iron redox cycling of the Fenton reaction and further trigger ferritinophagy. Subsequently, Zol coordinately exerted ferroptotic-inducing activity accompanied by induction of stimulator of interferon genes (STING) pathway to aggravate immunogenic cell death (ICD) and enhance the antitumor immune response. Furthermore, FTZ@Fu effectively attenuated the immunosuppressive TME to suppress tumor growth and distant metastasis, and FTZ@Fu potentiated the therapeutic efficacy in combination with immune checkpoint blockade (ICB) therapy. Importantly, FTZ@Fu SANs suppressed metastatic tumor growth and reshaped the immune microenvironment. Our nanosystem provides a promising avenue for synergetic cancer targeting and chemoimmunotherapy, paving the way for targeted therapeutic strategies.

Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy in recent years. In addition to rejuvenating anti-cancer immunity, ICI may cause immune dysregulation, impacting homeostasis, including brain functions. Thus, the association of ICI with cognitive function needs further investigation. Using NIH's PROMIS system, this study investigates self-reported cognitive impairment within a diverse cohort of ICI-treated patients. Additionally, we explore risk factors influencing self-reported cognitive function, including concurrent symptoms and racial/ethnic background.

Non-clinical pharmacological safety studies are conducted using cells and animals to ensure the safety of pharmaceuticals in humans. Following these studies, drug candidates are administered to humans during clinical trials. Safety must be sufficiently confirmed in non-clinical studies to ensure that test participants suffer no adverse health effects. However, due to species differences, low ability to extrapolate from in vitro to in vivo evaluation methods, and other problems, health hazards may unfortunately still occur. Therefore, sophisticated in vitro evaluation systems using human cells are actively being pursued. The main challenge remains the lack of a reliable methodology for extrapolating in vitro results to in vivo settings. We have attempted to extract parameters that can be predictably translated from in vitro [contractile evaluation in three-dimensional (3D) heart tissue] to in vivo (guinea pig echocardiography) conditions, using cardiac contractile dysfunction induced by anticancer drugs as an example. In this review, we introduce the in vitro methods developed to date to evaluate this cardiac contractile dysfunction, analyze the factors enabling highly accurate prediction of torsades de pointes in humans based on past proarrhythmic risk prediction methods using human induced pluripotent stem cell-derived cardiomyocytes, and apply them to evaluate cardiac contractile dysfunction caused by anticancer drugs using three-dimensional heart tissue. We also introduce the proposed strategy for this evaluation method in this section.

Autophagy has been implicated in the pathophysiology of thyroid cancer and in determining the response of cancer cells to anticancer therapy. Dabrafenib, a BRAF inhibitor, has demonstrated efficacy and safety in several types of cancers. However, it is unknown whether Dabrafenib exerts a protective effect on autophagy in thyroid carcinoma cells. In the current study, our findings demonstrate that treatment with Dabrafenib reduced cell viability and promoted LDH release in SW579 thyroid carcinoma cells. Dabrafenib was then shown to promote autophagy by increasing the level of Beclin1 and the LC3-II/LC3-I ratio while reducing the level of p62. Additionally, exposure to Dabrafenib upregulated the expression of HMGB-1 at both mRNA and protein levels. Interestingly, silencing of HMGB-1 abrogated Dabrafenib-induced autophagy, suggesting that the effects of Dabrafenib are mediated by HMGB-1. Further study revealed that Dabrafenib activated the JAK1/STAT1 signaling pathway and that blockage of the JAK1/STAT1 signaling pathway with its inhibitor Pyridone 6 ameliorated Dabrafenib-induced HMGB-1 upregulation and autophagy, implicating the involvement of the JAK1/STAT1 signaling pathway in this process. Collectively, these findings demonstrate that Dabrafenib induces autophagy in thyroid carcinoma cells via the JAK1/STAT1/HMGB-1 axis. Notably, this effect occurs independently of BRAF V600E mutation status, suggesting a novel therapeutic mechanism.

Ototoxicity, or hearing loss and damage to the auditory system caused by certain medications, is a significant clinical challenge. Many commonly used drugs, including antimicrobials, cancer therapies, and loop diuretics, have the potential to induce temporary or permanent ototoxicity. The underlying mechanisms are complex, involving both genetic and environmental factors. Pharmacogenomics, the study of how an individual's genetic makeup influences their response to drugs, has emerged as a promising field for understanding and mitigating ototoxicity. Developing personalized approaches to prevent and manage ototoxicity is crucial, and this is where the pharmacogenomic basis of ototoxicity becomes crucial. This review aims to provide healthcare professionals with an updated perspective on the genetics of ototoxicity by summarizing the latest research and insights in this rapidly evolving field. It presents a comprehensive overview of the mechanisms and genetic factors associated with drug-induced ototoxicity, with a particular focus on cisplatin and aminoglycoside antibiotics.

Age-related macular degeneration (AMD) remains the leading cause of blindness in developed countries. There are many different intravitreal anti-vascular endothelial growth factor (VEGF) drugs available for the treatment of neovascular AMD (nAMD). Unfortunately, not all patients respond equally well to the drugs, and some show recurrences during treatment. Since 01/2024, aflibercept 8 mg represents an additional treatment option and contains a four times higher dosage than the already known aflibercept 2 mg.

The study investigates the anticancer effects of green silver nanoparticles (Ag-NPs) synthesized from Viola cornuta extract combined with papaverine on breast cancer cells. Ag-NPs were characterized using various analytical techniques, confirming their presence with UV-vis spectroscopy showing a peak at 413 nm and an average size of 42 nm via field emission scanning electron microscopy (FE-SEM) analysis. The particles demonstrated a face-centred cubic structure, with energy-dispersive X-ray spectroscopy (EDX) confirming elemental composition. Additionally, the zeta potential measurement of -6.75 mV indicated favourable electrostatic repulsion between nanoparticles, thereby confirming their stability. Antioxidant activity was significant, with an EC50 value of 38.78 μg/mL. The combination treatment of Ag-NPs and papaverine exhibited synergistic effects, lowering IC50 values to 2.8 + 112.7 μg/mL for MCF-7 cells and 6.2 + 112 μg/mL for MDA-MB-231 cells, without toxicity to normal cells. Flow cytometry revealed G0/G1 phase inhibition and increased sub-G1 populations, indicating cell cycle arrest, alongside increased reactive oxygen species generation and apoptosis. Notably, the experimental group showed altered expression of oncogenic and tumour suppressor microRNAs and apoptotic genes (p < .0001), underscoring the potential of this nanoparticle-papaverine combination as an effective anticancer strategy against breast cancer treatment resistance.

Notoginsenoside Ft1 (NFt1) is a bioactive compound derived from Panax notoginseng, a traditional medicinal herb that exhibits various pharmacological properties, including anti-inflammatory and anticancer effects. However, its effects on hepatocellular carcinoma (HCC) remain poorly understood. This study sought to investigate the anticancer effects of NFt1 and uncover its fundamental mechanisms in HCC cells. NFt1 treatment inhibited cell proliferation and promoted apoptosis by enhancing cell death markers. Transcriptome profiling using RNA-sequencing revealed that NFt1 treatment downregulated the expression of oncogenes (e.g., FOS, BRAF, RARA, MYC, and JUND), while upregulating lysosomal cell death-related genes (e.g., CTSB, CTSD, LAMP1, LAMP2, and TPP1). These effects are associated with PI3K/AKT/mTOR inhibition and increased transcriptional activity of transcription factor EB (TFEB). NFt1 treatment induced autophagic traits by suppressing the PI3K/AKT/mTOR pathway, thereby enhancing TFEB transactivity. These findings demonstrated the therapeutic promise of NFt1 in the effective management of HCC.

Cardiac mitochondrial function is intricately regulated by various processes, ultimately impacting metabolic performance. Additionally, protein turnover is crucial for sustained metabolic homeostasis in cardiomyocytes.

Lung cancer is the leading cause of cancer deaths worldwide. Everolimus (Eve) was observed to upregulate the expression of phosphatase and tensin homolog and microRNA-4328 and inhibits the proliferation and migration of A549 cells. In the present study, a new nanocarrier based on composite containing chitosan (CS), carbon nanotubes (CNT) and ordered mesoporous (OMC) was used to load the anticancer drug everolimus (EVE). The existence of EVE on CNT/OMC/CS nanocarrier is confirmed by FE-SEM images, Raman, UV-Vis, FT-IR, BET and TGA analyses. The results showed that the introduction of CS improved the drug loading by 89.4% at pH 7.0, time 2 h and EVE to CNT/OMC/CS ratio of 1.5. Moreover, release study of EVE showed that 15.2% of EVE is released from EVE@CNT/OMC/CS at pH=7.4 for 15 h, while 78.9% of EVE is released at pH = 4.5. After 25 h, 16.8% and 88.0% of EVE were released at pH 7.4 and 4.5, respectively. Based on the MTT assay results, CNT/OMC/CS exhibited negligible cytotoxicity and good compatibility on the A549 lung cancer cell line. The cytotoxicity of the EVE@CNT/OMC/CS (IC50 of ~9 μg/mL) on the A549 cell line was higher as compared to free Eve drug (IC50 of ~13 μg/mL) after 48 h exposure time. All the data confirmed the synergistic effect of EVE in combination with CNT/OMC/CS could serve as an ideal candidate in treating lung cancer.

The majority of patients with melanoma develop immune-related adverse events (irAEs), and over half do not respond to anti-PD-1 (Programmed cell death protein 1) checkpoint inhibitor (CPI) immunotherapy. Accurate predictive biomarkers for both response to therapy and development of irAEs are currently lacking in clinical practice. Here, we conduct deep immunophenotyping of circulating regulatory and class-switched B cell and antibody immune states in patients with advanced stage III/IV melanoma prior to and longitudinally during CPI.

This study investigated the 3-year development of chemotherapy-induced peripheral neuropathy (CIPN) in post-menopausal women diagnosed with early breast cancer (EBC) using vibration perception threshold (VPT) measurements and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (CIPN18). 90 patients (aged 50-70) and 30 healthy subjects were included in the study. VPT measurements and CIPN18 questionnaires were performed post-chemotherapy (median 72 (IQR: 53-93) days post chemotherapy) as well as at the 12 and 36-month follow-up. Post-chemotherapy data showed impaired VPT measurements when comparing our study population to controls, but spontaneous improvement occurred, and by the 36-month follow-up, VPT measurements normalized when compared to controls. Mean CIPN18 scores improved, though the improvement was not statistically significant. Spearman's rho between VPT measurements and CIPN18 questionnaires showed weak to moderate correlations during follow-up. However, further analyses using a Generalized Additive Model confirmed the absence of a significant correlation between VPT measurements and CIPN18 questionnaires. Our data highlight limitations in the relationship between VPT measurements and CIPN. However, VPT measurements may have potential as an objective supplement to general assessment of patients.

Acute promyelocytic leukemia (APL) is highly malignant and progresses rapidly. In recent years, several studies have shown that oral arsenic, the primary component is realgar, could effectively alleviate APL, with therapeutic effects not inferior to those of intravenous arsenic and a higher safety profile, but currently the active substances and mechanism of realgar's anti-APL effect are unclear, making oral arsenic agents containing realgar lack sufficient scientific basis clinically. The clinical trials on oral arsenic agents containing realgar for the treatment of APL over the past 20 years were reviewed, suggesting it had good therapeutic effect and relatively high safety. Quantitative analysis was conducted on the accumulation of arsenic metabolites in different tissues during the longest 90 day period after realgar administration in rats, and it was found that dimethylarsenic (DMA) was the most predominant form of arsenic metabolites in the body. The DMA concentration slightly increased and remained stable with prolonged administration time, even if discontinuation, the DMA concentration still remained at a certain level. Distribution and accumulation of DMA were significantly higher in blood than in organs. Futhermore, DMA significantly prolonged the survival time of APL mice, induced cell apoptosis, inhibited NB4 cell proliferation, promoted the differentiation of leukemia cells, and downregulated the expression of PML-RARα fusion protein and wild-type RARα protein. The study concluded that DMA could be the main active substance of realgar and is responsible for its significant anti-APL effects, suggesting realgar has good efficacy for blood-related diseases and have low hepatorenal toxicity.

The KRAS (Kirsten rat sarcoma viral oncogene homolog) gene is recognized as the most frequently mutated oncogene in advanced non-small cell lung cancer (NSCLC). The most prevalent mutation within this gene is G12C, formally known as KRAS G12C, which leads to the substitution of glycine with cysteine at position 12 of the KRAS protein.

Despite their unique advantages and vast potential, nanomaterials employed in cancer therapy still encounter challenges such as uneven biodistribution, unintended drug leakage, and especially potential tissue damage caused by off-target toxicity. Bioinert nanomaterials, known for their excellent chemical stability, and minimal biological reactivity, can exert localized tumoricidal effects in response to specific external stimuli. However, the lack of precise control or poor penetration depth largely limits the therapeutic efficacy, necessitating the development of innovative stimuli-responsive therapeutic strategies. This study presents an alternative drug-responsive cancer therapeutic approach based on nickel-iron layered double hydroxide (NiFe-LDH), which exhibited negligible toxicity to both normal cells and cancer cells. By conjugating a platelet-derived growth factor receptor (PDGFR)-β-targeting cyclic peptide, NiFe-LDH achieved high specificity for prostate cancer cells, significantly enhancing tumor targeting and accumulation. Upon administration of deferoxamine mesylate (DFOM), an FDA-approved iron chelator, NiFe-LDH transitioned from a "bioinert" state to a "bioactive" nanotherapeutic through structural disassembly and robust release of nickel ions (Ni²⁺). The released ions disrupted mitochondrial function, upregulated insulin-like growth factor binding protein 3 (IGFBP3), and further inhibited the PI3K/AKT/mTOR signaling pathway, consequently leading to potent and selective induction of apoptosis in prostate cancer cells. Unlike conventional therapies, which often cause varying degrees of toxicity in non-target organs, this stimuli-responsive nanoplatform could minimize off-target effects and systemic toxicity by combining the non-toxic LDH with the clinically used DFOM. Our findings demonstrate that DFOM-responsive NiFe-LDH can effectively inhibit tumor growth in both cultured cells and tumor xenografts, suggesting a rational and clinically translatable platform for precision cancer therapy.