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.

The synthesis of the ligand 2-(2-methyl-4-hydroxyl)phenyl-1H-imidazo[4,5-f][1,10]phenanthroline (MHIP) and its corresponding new iridium(III) complexes [Ir(ppy)2(MHIP)]PF6 (ppy = 2-phenylpyridine, 9a), [Ir(bzq)2(MHIP)]PF6 (bzq = benzo[h]quinolone, 9b) and [Ir(piq)2(MHIP)]PF6 (piq = 1-phenylisoquinoline, 9c) was reported. The antiproliferative activity of compounds 9a-9c on HepG2, B16, and A549 cancer cells as well as on normal NIH 3T3 cells was tested using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was found that the three complexes showed moderate cytotoxicity in A549 and B16 cells. However, after further irradiation, the cytotoxicity was greatly enhanced; especially, 9a, 9b and 9c displayed significant cytotoxicity toward B16 cells with a low IC50 value of 3.1 ± 0.3 μM for 9a, 4.9 ± 0.8 μM for 9b, and 0.4 ± 0.1 μM for 9c. The effects of 9a-9c on the invasive ability of B16 cells were explored via colony formation and scratch experiments. Results demonstrated that the complexes could efficiently block cell proliferation and migration. The co-localization assay found that 9a-9c accumulated in the mitochondria and led to the apoptosis of B16 cells by decreasing mitochondrial membrane potential, altering the structure of microtubule proteins, damaging the structure of cellular DNA, and changing the expression of related proteins. The decrease in glutathione (GSH) concentration, the increase in malondialdehyde (MDA), the downregulation of GPX4, and C11-BODIPY staining results confirmed that 9a, 9b and 9c led to ferroptosis. In addition, we explored the relevant signaling pathways through an RNA sequencing assay and speculated on the possible anticancer mechanisms. Together, the results of this study indicate that the synthesized new iridium(III) complexes 9a-9c can induce cell death via ROS-mediated mitochondrial dysfunction, apoptosis and ferroptosis.

Monodisperse oligomers, positioned as intermediates between polymers and small molecules, retain certain reactivities of small molecules while simultaneously displaying the initial aggregation characteristics of the polymers. This distinctive structure bestows on them with significant potential for a wide range of applications. In this study, a series of carbolong osmium oligomers (Os1-Os4) and corresponding polymer were evaluated as photocatalysts. It was discovered that their molar absorption coefficients and reactive oxygen species generation rose with π-conjugation length, peaking at a polymerization degree of 4. Moreover, Os4 facilitates the photocatalytic oxidation of nicotinamide adenine dinucleotide (NADH) to its oxided form, NAD+. In vitro experiments demonstrated that Os4 had the strongest phototoxicity index in cells in hypoxic conditions, highlighting its potential efficacy in hypoxic tumor. Metabolomic analyses indicated that Os4 exerted its photocytotoxicity by disrupting purine metabolism. These insights will guide the future design of π-conjugated metal oligomers for advancing photocatalytic applications.

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.

Recently, we reported that the SARS-CoV-2 nucleocapsid (N) protein triggers DNA damage by inducing autophagic degradation of RNAi components (Dicer and XPO5) and splicing factors (SRSF3 and hnRNPA3). In this study, we found that the SARS-CoV-2 N protein synergizes with chemotherapeutics to induce DNA damage and activate the cGAS-STING pathway in NSCLC cells. Moreover, the SARS-CoV-2 N protein acts synergistically with chemotherapeutics to suppress the proliferation and colony formation of NSCLC cells. Finally, we demonstrated that the SARS-CoV-2 N protein enhances the antitumor effects of etoposide in xenograft tumor mouse model. These findings reveal a novel antitumor mechanism of the SARS-CoV-2 N protein, positioning it as a potential therapeutic agent for lung cancer patients.

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.

Most anticancer drugs exhibit low absorption rates in the intestines; therefore, Intravenous (IV) administration is employed, which increases the risk of side effects. In this study, we demonstrated the effectiveness of a novel delivery system, the Probiotic-derived Microcarrier (PM), which improves the oral absorption rate of poorly absorbed pharmaceutical drugs, including doxorubicin and paclitaxel. In a concentration of 1x1012 CFU of PM, doxorubicin accumulated to 3,512.6 μg, while paclitaxel reached 37.4 μg. When mice were administered PM-doxorubicin, the serum levels of doxorubicin significantly increased compared to those in mice that received doxorubicin alone. The enhanced bioavailability of doxorubicin was corroborated by the apparent anticancer effects of PM-doxorubicin observed in a mouse model. While orally administered doxorubicin did not exhibit antitumor efficacy, PM-doxorubicin demonstrated antitumor effects comparable to those of IV administration. The delivery of doxorubicin into the bloodstream via PM was facilitated by resident macrophages in the intestine, as evidenced by the observed interactions between PM and intestinal macrophages, as well as studies involving CSF-deficient mice. Our experimental findings indicate that the PM system can serve as an effective drug delivery vehicle, maximizing bioavailability through oral administration for drugs that are challenging to deliver orally, such as doxorubicin and paclitaxel.

Microtubules are important components of the cytoskeleton. Traditional Chinese medicines (TCMs), including Chinese ethnic medicines, such as Uighur medicines, Li ethnic medicines, Dong ethnic medicines, Lisu ethnic medicines, and Tujia ethnic medicines, can act on microtubules and tubulin, inhibit microtubule polymerization or promote microtubule depolymerization. In this paper, we review the microtubule-binding sites, summarize the mechanisms by which the active TCM and ethnic medicine ingredients and their derivatives inhibit microtubules, and look forward to applying TCMs and ethnic medicines to inhibit microtubules for cancer treatment.

Because aberrations of protein kinase activity play causal roles in several human diseases, this family of enzymes is one of the most important drug targets of the 21st century. Of the 88 protein kinase antagonists that are approved by the FDA, eleven of them form irreversible covalent complexes with their target enzymes. The clinical efficacy of ibrutinib, a Bruton tyrosine kinase blocker, in the treatment of mantle cell lymphoma following its 2013 approval helped to overcome a general bias against the development of irreversible drug inhibitors. Other approved targeted covalent inhibitors include acalabrutinib and zanubrutinib, which also block Bruton tyrosine kinase. Afatinib, dacomitinib, lazertinib, mobocertinib, and osimertinib inhibit members of the epidermal growth factor receptor family (ErbB1/2/3/4) and are used in the treatment of non-small cell lung cancers. Neratinib inhibits ErbB2 and is used in the management of ErbB2/HER2-positive breast cancer. Futibatinib blocks the fibroblast growth factor receptor family and is prescribed for the treatment of cholangiocarcinoma while ritlecitinib, which inhibits JAK3, is used in the management of alopecia areata. The eleven drugs considered in this review have a common mechanism of action involving the addition of a protein cysteine thiolate anion (proteinS:) to an acrylamide or an acrylamide-like derivative producing a thioether. The development of targeted covalent inhibitors is gaining acceptance as a valuable component of the medicinal chemist's toolbox and has made a significant impact on the development of protein kinase antagonists and receptor modulators.

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.

Isatin (1H-indole-2,3-dione) scaffold is an important heterocyclic building block which can be used for the design and synthesis of anti-cancer agents targeting tyrosine kinases, tubulin polymerization, carbonic anhydrases, and histone deacetylases. There are also several lines of evidences demonstrating the role of cyclin-dependent kinase 2 (CDK2) in cancer development and its potential as anti-cancer target. Here we are going to review isatin-derived CDK2 inhibitors and their potential for developing new anticancer agents. The purpose of this review is to present the importance of isatin scaffold for design of new CDK2 inhibitors from medicinal and biological viewpoints. Furthermore, the in vitro and in silico studies, and structure-activity relationships (SARs) were also discussed. The Insights derived from SARs provide crucial directions for the rational design of potent and selective isatin-based CDK2 inhibitors, which improve therapeutic efficacy and reduce side effects of anticancer chemotherapy.

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.

As a malignant tumor characterized by a dismal prognosis and a high mortality rate, non-small cell lung cancer (NSCLC) presents significant challenges in contemporary treatment. These challenges include drug resistance and side effects, which severely hamper the effectiveness of current therapeutic strategies. An increasing number of herbal formulas have been utilized in antitumor therapy, owing to their cost-effectiveness, beneficial efficacy, and additional advantages. FuZhengXiaoJi Decoction (FZXJD), a cancer-treating formula, has been successfully applied in NSCLC clinical treatment, but the underlying mechanism remains elusive. Therefore, this paper integrated multiple analytical methods, including network pharmacology, metabolomics, biological approaches, and molecular docking to clarify how FZXJD suppresses NSCLC.

Immune checkpoint blockade (ICB) is a tumor therapy that leverages the activation mechanisms of T cells in the immune system. A key challenge in ICB is poor T-cell infiltration and low tumor immunogenicity. Immunogenic cell death (ICD) can increase tumor immunogenicity and make tumors more sensitive to ICB. Programmed death ligand 1 (PD-L1) a major target for ICB. In this paper, a novel carbon nitride/methyl pyrophaeophorbide a‑copper/folate (abbreviated as CNMCF) nanocomposite was prepared for induced ICD. In CNMCF nanostructures, methyl pyrophaeophorbide a (MPPa) serves as the photodynamic therapy (PDT) agent, and copper ion serves as the chemodynamic therapy (CDT) agent. CNMCF not only induced ICD, but also alleviated tumor hypoxia. This led to down-regulation of hypoxia-inducing factor (HIF-1α) and PD-L1, promoted T lymphocyte invasion, effectively enhanced tumor immunogenicity, and elicited strong anti-tumor immune response, thereby suppressing primary tumor growth and metastasis. This research expanded the application of natural chlorophyll derivatives and C3N4-based drug delivery systems in cancer immunotherapy.