This study aimed to compare adverse event (AE) profiles between Avastin and bevacizumab biosimilars to support clinical decision-making, given the limited availability of real-world data.

Colorectal cancer is one of the deadliest forms of gastrointestinal cancer, with conventional treatments often facing significant limitations. As a result, new approaches, particularly in targeted drug delivery, have shown great promise. In this study, the COF-FA@DOX nanocarrier was developed, where covalent organic frameworks (COFs) were functionalized with folic acid (FA) and then loaded with Doxorubicin (DOX). The as-synthesized COF-FA@DOX nanocarrier was characterized using different techniques. To assess its anticancer effectiveness, MTT, flow cytometry, and scratch assays were conducted on SW480 and HUVEC cells to examine cell viability, cellular uptake, cell cycle progression, apoptosis, and cell migration, respectively. The obtained results demonstrated that the COF-FA@DOX nanocarrier was efficiently internalized by cancer cells and showed significantly higher cytotoxicity compared to other synthesized nanocarrier groups and free DOX drug. Moreover, the COF-FA@DOX nanocarrier caused cell cycle arrest, induced apoptosis, and inhibited cell migration at lower doses than the free DOX drug. Altogether, these findings suggest that the COF-FA@DOX nanocarrier is an effective and promising drug delivery system for DOX in colorectal cancer, potentially enhancing the therapeutic efficacy of DOX drug while minimizing side effects through targeted delivery. Further investigation is required to assess their efficacy in vivo and discover potential clinical applications.

Imatinib has been widely used in gastrointestinal stromal tumours and significantly improved the prognosis of GIST patients, but approximately half of patients develop acquired treatment resistance, highlighting the urgency for novel therapeutic strategies.

Small-cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis. Despite the initial chemosensitivity, survival for extensive-disease (ED) SCLC remains limited. Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have recently been redefined as the standard of care. We evaluated the efficacy of ICI combination therapy in clinical trials translated into real-world clinical practice for patients with ED-SCLC.

Spider silk is highly attractive material because of its superior mechanical properties and excellent biocompatibility, enabling it to self-assemble into a wide range of morphological structures for drug delivery system. However, most spider silk particles developed as drug carriers are based on complex repetitive domains of spider silk proteins and exhibit relatively large particle sizes (> 300 nm), which limits their biomedical applications. In this study, we engineered a novel recombinant spider silk protein (NC-iRGD) by integrating terminal domains derived from major ampullate silk and the tumor-penetrating peptide iRGD. The silk particles were generated by mixing with a high-concentration potassium phosphate buffer and exhibited an average particle size of approximately 170 nm, which is smaller than that of other reported spider silk particles. Under incubation of silk particles in the drug solution, a 90% loading efficiency for the peptide drug (ChMAP-28) were determined. The cytotoxicity result showed that NC-iRGD particles displayed excellent biocompatibility and high drug loading efficiency in the neutral pH and low ionic strength. The release of ChMAP-28 was shown to be dependent on the ionic strength and pH of the release buffer. Additionally, NC-iRGD demonstrated enhanced tumor penetration and greater cytotoxicity against cancer cells compared to NC particles due to its iRGD sequence. Overall, the high drug loading capacity, controlled-release capability, and improved tumor penetration of NC-iRGD particles make them a promising novel drug delivery system for targeting polypeptide therapeutics to tumor microenvironments.

This phase I trial aimed to assess the pharmacokinetics (PK), safety, and preliminary efficacy of a single dose of HR20013 (mixed formulation of fosrolapitant and palonosetron) plus dexamethasone in patients with malignant solid tumors.

Anticancer drug therapy-induced immunosuppression increases the incidence of treatment-resistant infectious diseases in cancer patients. Combining antibacterial and anticancer capabilities into a single medication can potentially enhance the treatment outcomes. In this light, the current study focused on developing innovative 5-arylidene-3-phenyl-2-thioimidazolones 1a-e and evaluated them as antimicrobial candidates against a panel of Gram-positive and Gram-negative bacterial and fungal isolates. Compounds 1e and 2d exhibited the most potent microbial activity, with MIC values ranging from 24 ± 0.5 to 12 ± 0.20 µg/ml in comparison with streptomycin and cycloheximide as reference standards. Using the colon cancer cell line (HCT 116) as a representative example, the novel compounds were assessed as anticancer agents. Compounds 1e and 2d appeared to be the most effective candidates, with IC50 values of 7.25 ± 1.03 and 44.3 ± 3.28 µg/ml, respectively, when compared to doxorubicin (IC50 = 4.12 ± 0.50 µg/ml). Therefore, we extended the anticancer study of both 1e and 3b to include the other three cancer cells, PC3, A549, and MCF-7, and the normal Vero cell line. 1e was the most effective anticancer compound, exhibiting IC50 values ranging from 5.2 ± 0.09 to 8.1 ± 0.11 µg/mL and demonstrating a promising safety profile against the BJ1 normal cell line. In vitro enzyme screening assay of 1e against CDK-2, EGFR, HER-2, and VEGFR-2 enzymes investigated its promising multitargeting inhibiting activity (IC50 = 0.314 ± 0.031, 0.183 ± 0.014, 0.197 ± 0.024, and 0.235 ± 0.028 µM, respectively). A molecular docking study was carried out to discover the probable interactions of compound 1e with the active sites of the assessed kinases. Additionally, in silico ADMET studies were carried out for 1e, which represented its good oral absorption, good drug-likeness characteristics, and low toxicity risks.

Recently, essential oils (EOs) have garnered attention for their biological properties as a source of natural compounds with anticancer and antioxidant effects. Artemisia herba alba grows commonly on the dry steppes of the Mediterranean regions in Northern Africa, Western Asia, and Southwestern Europe. This species is native to Palestine and the western region of Jordan, known as Sheeh. It is employed by the Bedouins for the remedy of many diseases. Recently, essential oils (EOs) have been booming with a growing interest in their use as palliative treatments to conventional medicine due to their biological qualities. The objective of this study is to identify the chemical composition of EO extracted from the dry leaves of A. herba alba and to evaluate their in vitro antioxidant, anticancer, and α-amylase and lipase inhibitory activity. The EO was extracted via hydrodistillation and examined using gas chromatography-mass (GC-MS) spectrometry to determine its chemical composition. The primary components included 1,8-cineole (28.67%), followed by trans-thujone (24.00%), cis-thujone (17.69%), camphor (12.76%), and concluding with terpinen-4-ol (8.34%). Biologically, the EO performed high antioxidant activity against 1,1-diphenyl-2-picrylhydrzyl (DPPH) with 22.17 ± 1.11 µg/mL and modest lipase and α-amylase activity. The EO displayed significant anticancer properties against B16F10 and MCF-7 with IC50 values of 12.39 and 13.60 µg/mL, respectively. A 1:1 combination of Artemisia herba alba and Teucrium polium EOs improved the anticancer activities against B16F10 and MCF-7 cell lines, with IC50 values of 6.184 and 9.427, respectively. Adding 25-50 µg/mL to Taxol (10 ng) caused a remarkable increase in the inhibition of cancer cells. This enhancement in cancer cell inhibition suggests a potential synergistic effect between the essential oil and Taxol, warranting further investigation into their combinatory use in therapeutic applications. Future studies may explore the underlying mechanisms of this synergy to optimize treatment strategies for cancer patients.

The aim of this research was to prepare a different particle sizes of zinc oxide nanostructures by two different methods. The zinc oxide nanoparticle (ZnO NPs) was successfully prepared by a green synthesis technique but the zinc oxide quantum dot (ZnO QDs) was successfully prepared by a chemical method. The structure, composition and morphology of the prepared different shapes of ZnO nanostructures have been characterized by the means of X-ray diffractograms (XRD), high resolution transmission electron microscope (HRTEM), Energy Dispersive x-ray (EDX), UV-Vis spectroscopy and Fourier transform infrared spectroscopy (FTIR). From UV-Vis spectroscopy studies we noticed that the optical band gap energy of ZnO nanostructures was decreased by increasing an irradiation time. The removal of complex organic contaminants and pollutants from water, the heterogeneous photocatalytic degradation of methylene blue (MB), Fluorescein and Rhodamine 6G (Rh 6G) dyes were studied using ZnO NPs and ZnO QDs as a derived catalyst. We had studied the impact of ZnO NPs and ZnO QDs as a catalyst to enhance the photocatalytic activity of different organic dyes under UV-Vis irradiation and we observed that the photodegradation percentage of organic dyes was rapidly increased by increasing UV irradiation time in both two shapes of ZnO nanostructures. ZnO QDs behave as the best photocatalyst for successfully photodegraded due to the smallest size of ZnO QDs has a higher photocatalytic activity than the large particle size of ZnO NPs. So, it is better to use the ZnO QDs as a removal dyes and pollutants in the wastewater application. Also, we have assessed the cytotoxicity of ZnO NPs and ZnO QDs against two cell lines, (T-47) breast cancer carcinoma, and (DU-145) prostate cancer cell compared to Human skin fibroblast (HSF). The proliferation of cancer cells using MTT assay clarified that both cancer cells (T-47), (DU-145) as well as (HSF) normal cell line are regularly inhibited as they grow on different concentrations of ZnQ QDs and ZnQ NPs. The maximum inhibitory effect of both were recorded at concentration of 100 µg/ml (62.63, 79.72 and 42.59% and 72.68, 83.28, 18.12 µg/ml) in case of ZnQ QDs and ZnQ NPs respectively. It was cleared that ZnQ NPs was more potent for test cancer cell lines, this was confirmed by IC50, since it was (18.12,13.3,74.86) in ZnO NPs compared with (42.59,17.05 and 76.4) in ZnQ QDs respectively. Finally, it was proved that the ZnO NPs behave as a good anticancer nanomaterial than ZnO QDs. This means ZnO NPs are superior for anticancer applications if compared with ZnO QDs.

Cancer is characterized by abnormal cell proliferation. Cyclins and cyclin-dependent kinases (CDKs) have been recognized as essential regulators of the intricate cell cycle, orchestrating DNA replication and transcription, RNA splicing, and protein synthesis. Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers, rendering cyclins and CDKs attractive therapeutic targets. Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use, fueling the development of CDK-targeted therapies. With this enthusiasm for finding novel CDK-targeting anti-cancer agents, there have also been exciting advances in the field of targeted protein degradation through innovative strategies, such as using proteolysis-targeting chimera, heat shock protein 90 (HSP90)‍-mediated targeting chimera, hydrophobic tag-based protein degradation, and molecular glue. With a focus on the translational potential of cyclin- and CDK-targeting strategies in cancer, this review presents the fundamental roles of cyclins and CDKs in cancer. Furthermore, it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs, detailing the underlying mechanisms of action for each approach. A comprehensive overview of the structure and activity of existing CDK degraders is also provided. By examining the structure‍‒‍activity relationships, target profiles, and biological effects of reported cyclin/CDK degraders, this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.

Anti-programed cell death protein-1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies combined with anti-vascular endothelial growth factor (VEGF) or anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies are now standard therapeutic options for patients with treatment-naïve, advanced stage, hepatocellular carcinoma. Given the observed efficacy in the advanced setting, the unmet need for therapies for intermediate stage liver cancer, and compelling preclinical rationale for combination with liver-directed therapies, such as transarterial chemoembolization, immunotherapies have quickly moved into earlier stages of the disease. Several phase 1/2 clinical trials have collectively verified the safety of immune checkpoint blockade with regional therapy for intermediate stage, liver-limited, hepatocellular carcinoma. Recently, two global, randomized, double-blind, placebo-controlled studies have demonstrated superior efficacy, based on the surogate of progession free survial, for transarterial chemoembolization plus combination immunotherapy over chemoembolization alone. In this issue of the Journal, Li and colleagues present data for an anti-PD-1 inhibitor with chemoembolization in liver-limited hepatocellular carcinoma (HCC). This study, along with the status of the field, provides the opportunity to highlight key issues for implementation of combinatorial approaches in patients with liver-limited liver cancer, which are discussed in this Commentary. Regional treatment with immune checkpoint inhibition combinations for intermediate stage disease is now rightly at the forefront of HCC drug development, though specific biologic factors, ideal patient characteristics, and optimal combinations require deeper investigation prior to routine use for all patients.

Cancer immunotherapy targeting the PD-1/PD-L1 pathway has demonstrated efficacy across a range of common solid tumors and some hematopoietic malignancies. Despite these groundbreaking successes, the clinical development of other 'checkpoint inhibitors' targeting molecules like TIM-3, TIGIT, ICOS and others, has largely fallen short, often showing minimal clinical benefit even in combination with anti-PD therapy. This article explores three key hypotheses that help explain the disparity in therapeutic success: (1) the absence of tumor- specific immunosuppressive logic in many checkpoint targets, (2) the dominance-but not redundancy-of immune evasion mechanisms within the tumor microenvironment (TME), and (3) the emergence of therapy-induced resistance. This is not intended as a comprehensive review of the literature. Instead, it highlights select evidence to explain past failures and to illuminate a more strategic, biologically informed path forward.

Cancer is an age-related disease that affects one in two Japanese individuals, placing a significant burden on both patients and caregivers due to its clinical characteristics, high treatment costs, and associated adverse events (AEs). Consequently, cancer treatment remains a major public concern. In recent years, patient-centered medical care has gained increasing attention and is strongly desired in cancer treatment. Companion diagnostics (CDx) are expected to facilitate personalized treatment; however, their current status remains unclear. In this study, we evaluated the role of CDx in anticancer drug treatment based on data available at the time of drug approval. Our analysis revealed that the benefit-risk ratio, defined as the objective response rate of an anticancer drug divided by the incidence of severe AEs, was significantly higher for anticancer drugs requiring CDx (wCDx) in Japanese patients (1.54-fold, p < 0.0135) than for anticancer drugs not requiring CDx. Although the objective response rate did not differ between the 2 groups, the incidence of severe AEs was lower in the wCDx group. These findings suggest that CDx helps identify patients who are better suited for specific anticancer treatments and/or that active pharmaceutical ingredients in wCDx therapies carry a lower risk of severe AEs. To further promote patient-centered medical care, the active development of CDx alongside new anticancer drugs should be encouraged, despite the higher development hurdles, through regulatory support, particularly since drug pricing does not differ between the 2 groups.

Pigmentation is one of the most prominent side effects caused by anticancer drugs, especially in female patients, as these changes in appearance can decrease QOL. A typical drug causing such pigmentation is 5-fluorouracil (5-FU); we have previously shown that 5-FU-induced pigmentation is associated with increased adrenocorticotropic hormone (ACTH) and reactive oxygen species (ROS) levels. In male Hos:HRM-2 mice, 5-FU administration resulted in pigmentation appearing in the genital area, accompanied by elevations in neutrophils, ACTH, and ROS. By contrast, female mice showed increases in neutrophils and noradrenaline, but not in ACTH or ROS levels; furthermore, they did not develop pigmentation. In addition, estradiol levels were markedly decreased in female mice, which may have enhanced neutrophil apoptosis and suppressed ROS production. In addition, noradrenaline reflects the stress response and may contribute to the decrease in estradiol, suggesting the hypothalamus-pituitary-adrenal axis and sex hormones may interact in the formation of sex differences. These results suggest that sex differences exist in the development of 5-FU-induced hyperpigmentation and that fluctuations in estradiol and associated changes in neutrophils, ROS, and ACTH may underlie this phenomenon.

The location of nasopharyngeal carcinoma (NPC) is relatively hidden. Most patients are diagnosed at the middle or late stage of the disease, having missed the best time for treatment.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer death worldwide. Sonodynamic therapy (SDT) offers a non-invasive, deep-penetrating approach by using ultrasound to activate sonosensitizers and generate cytotoxic reactive oxygen species (ROS). Yet poor intratumoral delivery and low ROS quantum yields of existing agents have stalled clinical translation. Here, we present a synergistic SDT platform that overcomes these barriers by combining transient vasodilation of tumor microvessels with the clinically widely used Antianginal drug isosorbide mononitrate and an acceptor-donor-acceptor-donor-acceptor type organic nanosonosensitizer (BTz) engineered for a narrow bandgap and enhanced ultrasound responsiveness. Isosorbide mononitrate increases nanosonosensitizer accumulation by ~ 1.8-fold. Under ultrasound irradiation, nanosonosensitizer produced high ROS generation, resulting in 78% tumor growth inhibition in murine HCC models-nearly double that of SDT alone-without detectable systemic toxicity. Crucially, the near-infrared fluorescence of nanosonosensitizer enabled real-time, image-guided tracking of sonosensitizer uptake and therapeutic response. By repurposing a safe vasodilator and integrating it with a high-performance organic sonosensitizer, this work establishes a readily translatable, minimally invasive paradigm for precise SDT of localized, inoperable or metastatic HCC.

The combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has played a significant role in the improvement of tumor therapy, but the increased incidence of pneumonitis has greatly limited its application. To identify potential intervention targets, we analyzed risk factors for pneumonitis after combination therapy with ICIs and TRT.

Doxorubicin is an antitumor antibiotic. It is often used in veterinary medicine to treat and extend the lives of dogs with cancer. A cardiotoxic side effect can lead to heart failure and treatment discontinuation. This systematic review and meta-analysis aimed to evaluate the drug's cardiotoxic effects on the ejection fraction (EF) of dogs in doxorubicin protocols. The search was done in eight databases, with a total of 3587 articles screened, resulting in fifteen eligible articles included. A report on the included studies' methods and results was done. It also assessed the risk of bias. Thirteen articles demonstrated cardiac changes in echocardiography with different routes of administration (intravenous and intracoronary). The intracoronary route was more toxic, and in all six studies performed, there was heart failure. The intravenous route caused heart failure in six of the nine studies. A meta-analysis showed this drug worsened heart disease. It included four studies where it significantly lowered the EF. Overall, the intervention produced a mean reduction of 21.24% in EF. This review shows doxorubicin's impact on cardiac function. It reveals the need for careful monitoring of each patient.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with limited effective therapeutic options due to late diagnosis, aggressive progression, and rapid development of drug resistance. In pursuit of novel treatments, this study reports the design, synthesis, and biological evaluation of a new series of topsentin derivatives, featuring a 1,2,4-oxadiazole core. The newly synthesized derivatives were screened for antiproliferative activity against multiple PDAC cell lines (SUIT-2, Patu-T, and PANC-1), identifying several compounds with potent growth-inhibitory effects, particularly on SUIT-2 and Patu-T cells. Further studies demonstrated that these compounds also significantly inhibited cell migration and reduced clonogenic potential, with IC50 values in the micromolar range. The results suggest that these marine-inspired 1,2,4-oxadiazole derivatives effectively target key hallmarks of PDAC, including proliferation, migration, and colony formation, supporting their further development as promising candidates for overcoming drug resistance and metastatic progression in pancreatic cancer.

Microbial exopolysaccharides from extreme environments are increasingly becoming valuable candidates for drug development. In this study, four fractions named XL-1, XMRS-1, XL-1-D, and XMRS-1-D were isolated and purified from the hadal bacterium Psychrobacter pulmonis by column chromatography. The structural features of these fractions were characterized by molecular weight, monosaccharide composition, Fourier transform infrared (FTIR) spectrum, amino acid analysis and NMR. The results showed that XL-1 and XMRS-1 were mainly composed of mannose, glucose, and glucosamine, while XL-1-D and XMRS-1-D were mainly composed of mannose. In vitro bioactivity assays demonstrated that all four fractions significantly enhanced RAW264.7 macrophage proliferation and phagocytosis, stimulated nitric oxide (NO) and reactive oxygen species (ROS) production, and induced the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and the expression of inducible nitric oxide synthase (iNOS) mRNA. Moreover, plate cloning tests, cell scratch tests, and apoptosis assays, along with RT-qPCR analysis, demonstrated that the four fractions significantly inhibited A549 cells' proliferation. Specifically, XMRS-1 and XMRS-1-D upregulated Bax, Caspase-3, Caspase-8, and Caspase-9, while downregulating Bcl-2, suggesting transcriptional activation of apoptosis-related pathways. These results offered a reference for the further development and utilization of this hadal bacterium in the future.