Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of malignant melanoma; however, they are frequently associated with immune-related adverse events (irAEs). Emerging evidence suggests that genetic predispositions, including interleukin-7 (IL-7) gene variants, may influence the risk of these toxicities.

The impact of H. pylori infection on the efficacy of trastuzumab in HER2-positive gastric cancer (GC) remains poorly understood, despite growing evidence that tumor microenvironment and host-pathogen interactions influence therapeutic outcomes. This study aimed to investigate how H. pylori strains of differing virulence, one high (HV-HP) and one low (LV-HP), affect GC cell behavior, particularly in the context of ERBB2 (HER2) amplification and Trastuzumab (TRAS)-resistance.

The incorporation of immune checkpoint inhibitors (ICIs) into cancer treatment has revolutionized oncology, providing marked advantages in managing various types of cancer. Nevertheless, the increasing use of ICIs has led to the emergence of immune‑related side effects, including autoimmune diseases such as inflammatory arthritis. IL‑6 signaling is crucial in the development of inflammatory arthritis and is linked to both the benefits and adverse effects of ICIs. The present review summarizes the latest progress in the IL‑6 pathway in inflammatory arthritis and discusses the therapeutic potential of IL‑6 pathway inhibitors for ICI‑induced inflammatory arthritis.

The aim of the present study was to investigate the direct effects of BMS‑202 on melanoma cells. The small molecule programmed cell death ligand 1 (PD‑L1) inhibitor BMS‑202 was used to treat A375 melanoma cells. The cell distribution of BMS‑202 was examined using low‑power and high‑resolution confocal microscopy, focusing on its localization in mitochondria. The impact of BMS‑202 on mitochondrial gene expression levels, the activity of respiratory chain complexes, and the levels of reactive oxygen species and apoptosis‑related genes, including Bax, Bcl‑2, PARP and caspase‑3, were assessed by quantitative PCR and western blotting. Additionally, tumor cell viability, proliferation, migration and invasion were evaluated in vitro, with in vivo experiments conducted through the construction of tumor‑bearing mouse models and Ki‑67 immunohistochemical staining to validate tumor proliferation. The function of mitochondria was inhibited using a pyruvate carrier inhibitor to examine how this affected the action of BMS‑202. The results revealed that BMS‑202 can inhibit tumor cell function and promote apoptosis. Furthermore, BMS‑202 was shown to enter the mitochondria where it may bind to PD‑L1 and improve mitochondrial function. By inhibiting mitochondrial function, the antitumor effects of BMS‑202 can be enhanced. Overall, the present study provides information on the potential antitumor mechanisms of BMS‑202 as well as a theoretical basis for its application in melanoma therapy.

In this review, the role of microRNA‑21 (miRNA‑21) as an oncogene in lung cancer was investigated. Studies have shown that miRNA‑21 can promote the progression of lung cancer by targeting downstream target genes, and its expression can be modulated by transcription factors, DNA methylation or competitive endogenous RNA as an upstream regulator. This review highlights that miRNA‑21 can promote the progression of lung cancer through multiple signaling pathways, with a focus on the PI3K/AKT, MEK/ERK, TGF‑β/SMAD, Hippo, NF‑κB and STAT3 signaling pathways. Mechanistically, miRNA‑21 plays an important role in the progression of lung cancer by regulating multiple biological processes, such as proliferation, invasion, metastasis, apoptosis and angiogenesis in lung cancer cells. Higher expression of miRNA‑21 is associated with chemotherapy, radiotherapy and immune resistance in lung cancer. Targeting these molecular pathways may be a novel therapeutic strategy for treating lung cancer. Additionally, miRNA‑21 can serve as a biomarker for lung cancer diagnosis, prognosis and treatment response. This review also summarized the following: i) Current methods employed to inhibit the expression of miRNA‑21 in lung cancer, including CRISPR/Cas9 technology; ii) the application of natural anticancer agents, oligonucleotides, small molecules and miRNA sponges; and iii) the nano‑delivery systems developed for miRNA‑21 inhibitors. Finally, the advancements in research on miRNA mimics and inhibitors in clinical trials, which may promote the application of miRNA‑21 in clinical trials in lung cancer, were discussed. Given that lung cancer is a considerable public health challenge, these studies provide new ways of treating patients with lung cancer.

This study reports a green, efficient, and high-yielding synthesis of novel imidazole derivatives 5a-i via a one-pot, four-component reaction under microwave irradiation. The optimized protocol demonstrates satisfactory yields (86%-92%), short reaction times (9-14 min), easy workup, and avoidance of toxic solvents, in accordance with sustainable chemistry principles. The antiproliferative efficacy of derivatives 5a-i was evaluated against H1975, A549, and A431 cells, using the MTT assay. The results indicated that derivatives 5b and 5g exhibited the greatest antiproliferative activity, with IC50 values of 5.22 and 6.34 µM. The values obtained were markedly inferior to those of recognized EGFR inhibitors, such as osimertinib, gefitinib, and erlotinib. Compound 5b was exhibited as the most potent inhibitor of both EGFRWT and EGFRT790M kinases, with IC50 values of 30.1 and 12.8 nM, respectively. The findings exceeded those of osimertinib and gefitinib, which demonstrated IC50 values of 54.3, 19.1, 9.1, and 356.8 nM, respectively, which may explain its notable antiproliferative effect against the H1975 cell line. Molecular docking and dynamics simulations confirmed the stable binding of derivatives 5b and 5g within the EGFR active sites, aligning with experimental findings. Furthermore, in silico ADME properties for the promising EGFR inhibitors 5b and 5g, conducted using the egg-boiled technique, demonstrated favorable lipophilicity, G.I.T. absorption, and BBB permeability. As a result, imidazoles 5a-i, particularly 5b and 5g, exhibited promising antiproliferative properties, targeting EGFRWT and EGFRT790M kinase inhibitors.

Phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in the de novo Serine synthesis pathway (SSP), a highly regulated pathway overexpressed in several tumors. Specifically, PHGDH expression is dynamically regulated during different stages of tumor progression, promoting cancer aggressiveness. Previously, we demonstrated that high Serine (Ser) availability, obtained by increased exogenous uptake or increased PHGDH expression, supports 5-Fluorouracil (5-FU) resistance in colorectal cancer (CRC). Beyond its metabolic role in sustaining Ser biosynthesis, different "non-enzymatic roles" for PHGDH have recently been identified. The present study aims to investigate non-enzymatic mechanisms through which PHGDH regulates 5-FU response in CRC.

Unresectable hepatocellular carcinoma (uHCC) with portal vein tumor thrombosis (PVTT) has poor prognoses. This study evaluated the efficacy and safety of lenvatinib (LEN) combined with anti-PD-1 antibodies (PD-1) and locoregional therapy (LRT) in uHCC patients with PVTT.

Chemotherapy-induced peripheral neuropathy (CIPN), hand-foot syndrome (HFS), and nail changes are common adverse effects associated with chemotherapy, significantly impacting the quality of life of cancer patients, and effective interventions remain an unmet need in oncologic care. Regional limb cooling is an emerging non-pharmacological approach used to prevent or reduce the severity of these adverse side effects. Although the awareness of regional limb cooling is rather prevalent, the overall use and efficacy of this non-pharmacological therapy in preventing chemotoxicities is not universally agreed upon. This paper reviews the current evidence regarding the use, efficacy, limitations, and safety of regional limb cooling in preventing or reducing CIPN, HFS, and nail changes in clinical settings.

The increasing global incidence of cancer emphasizes the vital role of machine learning algorithms and artificial intelligence (AI) in identifying novel anticancer targets and developing new drugs. Computational approaches can significantly quicken research on complex disorders, enabling the discovery of effective treatments. This study explores anticancer targets by assessing the potential of naturally occurring compounds derived from various plants to cure colorectal cancer. Twenty compounds were sourced from PubChem, and the RPS20 protein structure was obtained from AlphaFold, and mutation "V50S" was added. Validation of mutated RPS20 protein was performed using the Ramachandran plot and ERRAT. Binding sites on the mutated RPS20 protein were identified with DeepSite, followed by virtual screening to pinpoint the most promising natural lead drug candidate. Indirubin emerged as the lead drug candidate, fulfilling all ADMET criteria and exhibiting a good binding affinity. Further development included designing an AI-based drug using the WADDAICA server, which was validated through molecular docking, molecular dynamics (MD) simulation, and MMGBSA. The electronic properties of indirubin were studied using DFT calculations. The results show a moderate HOMO-LUMO gap, indicating its potential reactivity and the possible capability for biological target interactions. These findings indicate that indirubin could serve as a potent and effective cancer inhibitor, offering high efficacy with minimal side effects.

Triple-negative breast cancer (TNBC) is the most aggressive among the breast cancer subtypes and poses unique therapeutic challenges due to its distinct characteristics like lack of specific therapeutic targets. TNBC demonstrates poor survival rate enhanced immunogenic characteristics and a more favorable tumor microenvironment than other breast cancer variants. Also, TNBC patients show elevated levels of programmed death ligand-1 (PD-L1) expression in contrast to non-TNBC patients. Binding of PD-L1 with PD-1 produces an inhibitory signal, resulting in suppression of T-cell. Therapeutic approaches utilizing immunotherapies against PD-L1 exhibit promising outcomes in the treatment of TNBC. Limitations like suboptimal efficacy, inadequate oral bioavailability, and associated immune-related adverse effects of antibody-mediated anti PD-1/PD-L1 therapies have necessitated the exploration of alternative therapeutic approaches. Thus, small molecules become an alternate option for PD-1/PD-L1 inhibition. In the present study, we have used virtual screening to identify potential phytochemicals from selected Indian medicinal plants as PD-L1 inhibitors. A total of 953 phytochemicals derived from eleven selected medicinal plants were initially screened through molecular docking using the PyRx tool. Among the 953 identified phytochemicals, the top 20 compounds exhibiting the highest binding affinities in docking study were selected for further analysis. Following comprehensive ADMET analyses, 2 compounds were ultimately identified as suitable candidates for a molecular dynamics (MD) simulation study. The study identified 4-hydroxychalcone and flavylium from Glycyrrhiza glabra and Catharanthus roseus, respectively as potential PD-L1 inhibitors with enhanced stability relative to the reference molecule. Both compounds also showed enhanced gastrointestinal absorption with no predicted cytotoxic and immunotoxic effects. Consequently, these compounds present promising candidates for novel PD-L1 inhibitor development in TNBC therapy. Further experimental investigations are necessary to facilitate their clinical translation.

Resveratrol is a natural compound with notable health benefits, such as anti-inflammatory, antioxidant, and chemopreventive properties. It has shown potential in inhibiting tumorigenesis and tumour progression via targeted therapy, specifically by targeting cancer stem cells (CSCs). CSCs are a small, self-renewing subpopulation within tumours that drive cancer progression and are marked by biomarker proteins such as CD133, CD44, Sox2, Nanog, Oct4, ABCG2 and ALDH1. Effective treatment requires direct targeting of these cells. Understanding the pathways that govern CSC formation and their response to resveratrol is crucial for optimizing therapy. While extensive research exists on resveratrol's effects in cancers like glioblastoma, breast, and colorectal, studies on its effects in lung cancer stem cells (LCSC) remain limited. This review aims to fill this gap by exploring resveratrol's impact on CSC across various cancers and hypothesizing its mechanisms in lung cancer stem cells (LCSC). By synthesizing findings from other cancer types, we aim to outline potential pathways resveratrol may target in lung CSC as well as to elucidate any interconnectedness between these signalling pathways.

Twenty-one novel quinazolin-4(3H)-one derivatives were synthesized and evaluated for their cytotoxic effects against the PC3 prostate cancer cell line. Structural characterization was performed using FTIR, NMR, and HRMS spectroscopy. Cytotoxicity assays revealed that compound 1 exhibited the highest potency (IC50 = 4.29 ± 0.32 µM) and selectivity (SI = 20.1) against PC3 cells, surpassing the reference drug sorafenib. Compounds 10 and 11 also demonstrated significant selectivity (SI = 12.7 and 12.4, respectively), making them promising candidates for further investigation. Molecular docking studies confirmed strong binding affinities to the androgen receptor (AR), with compound 1 displaying the most favorable interaction (IFD Glide Score = -15.137 kcal/mol, MM-GBSA = -72.11 kcal/mol). MD simulations further supported the stability of compound 1 within the receptor binding site, highlighting key hydrogen bonding and π-π stacking interactions. ADME predictions indicated favorable pharmacokinetic properties, with all active compounds complying with drug-likeness criteria and exhibiting high oral absorption. Overall, these findings suggest that quinazolinone derivatives, particularly compound 1, hold significant potential as selective anticancer agents targeting prostate cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, significantly improving outcomes for various malignancies. Despite their clinical success, only a subset of patients benefits from ICIs treatment, underscoring the need for innovative strategies to enhance their therapeutic potential. Ferroptosis, a unique form of programmed cell death driven by iron-dependent lipid peroxidation, has emerged as a promising partner for enhanced immunotherapy. Combining ferroptosis inducers with immune checkpoint blockade has shown promising potential in improving the efficacy of cancer immunotherapy. This study explores the mechanisms of ferroptosis and immune checkpoint inhibitors for synergistic cancer treatment, and reviews recent delivery platforms integrating ferroptosis and immune checkpoint blockade for enhanced therapy.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers like malignant melanoma. However, they can lead to a range of immune-related adverse events (irAEs), impacting various organ systems. Among these, myositis is a rare but serious irAE, typically characterized by myalgia, muscle weakness, and elevated creatine kinase (CK) levels. Herein, we report the case of a 58-year-old female with advanced melanoma, who presented a delayed-onset of ICI-induced myositis accompanied by severe muscle weakness. Interestingly, the CK levels remained normal throughout her disease course. Neurological examination, MRI, and electromyography were pivotal in diagnosing myositis. Differential diagnoses, including myasthenia gravis, myocarditis, and paraneoplastic syndromes or idiopathic inflammatory myopathies, were systematically ruled out through clinical evaluation, serological testing, and imaging. The patient responded favorably to high-dose corticosteroid therapy, leading to a gradual improvement of symptoms and no relapse after stopping treatment. This case report emphasizes a multimodal diagnostic approach and underscores the importance of clinical awareness for such atypical irAE presentations.

Pembrolizumab is a monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor pathway, which has increasingly been implicated in cancer treatment regimens. Since its first approval for melanoma in 2014, many trials have investigated the efficacy and safety of this new drug in different cancers. In this review, we discuss the therapeutic advances achieved with pembrolizumab in the management of eight cancers that are associated with a relatively poor prognosis. We also report the FDA approvals of this drug, highlighting promising ongoing trials and potential aspects for future research.

Previous studies have shown that Ras-Related Nuclear Protein (RAN), a member of the RAS superfamily, is a small GTPase and an important oncogene in several cancers. However, its role in multiple myeloma (MM) and its potential contribution to drug resistance remain undetermined. Bioinformatics was employed to analyze differentially expressed genes in MM samples. RT-qPCR and western blotting were utilized for protein transcription and expression analysis. The CCK-8 assay was adopted to evaluate cell proliferation, and in vivo animal experiments were conducted to validate the results. The findings reveal that RAN represents one of the most significantly aberrant genes in MM, with its expression significantly elevated in both MM tissues and cells. Genetic manipulation experiments demonstrated that RAN promotes MM cell proliferation by activating the Wnt/PCP pathway. Concurrently, RAN governs the response of MM cells to the anti-cancer drug bortezomib (BTZ). Knockdown of RAN leads to increased sensitivity to BTZ. Mechanistic studies indicate that RAN influences drug response by regulating the activation of the JNK/c-Jun axis, thereby affecting the therapeutic response of MM cells. In summary, the upregulated expression of RAN in MM leads to BTZ resistance via activation of the Wnt/PCP pathway, potentially serving as a novel therapeutic target for MM.

This study investigated the efficacy and safety of first-line afatinib treatment in older patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).

Topical therapy with imiquimod in a cream [5% w/w imiquimod cream (Aldara™)] for the treatment of nodular basal cell carcinoma (BCC) currently results in low cure rates, attributed to low imiquimod permeation. Herein we have developed novel microneedle array patches (MAPs), to maximize imiquimod intradermal delivery and retention in the skin, with potential as an efficacious treatment for BCC. Enhanced delivery of imiquimod in pig skin and ex vivo BCC tissue was found with the obelisk poly N-acryloylmorpholine (pNAM) MAPs as compared to the 5% w/w imiquimod cream and MAPS manufactured from a commercially available polymer (PVPVA). Additionally, the increased retention in ex vivo BCC tissue was found with the obelisk pNAM MAPs as compared to the 5% w/w imiquimod cream. In addition, detailed characterization of single needles and mechanistic studies of MAPs in tissue using mass spectrometry imaging confirmed the imiquimod homogeneity in the needles. Most importantly, the in vivo tumor efficacy study showed that pNAM obelisk MAPs could deliver imiquimod into the tumor, retarding tumor growth. This study suggests that the drug loaded obelisk pNAM MAPs manufactured here may be of clinical utility for localized intradermal delivery of imiquimod.

Immune checkpoint inhibitor (ICI) has reshaped the treatment landscape of esophageal squamous cell carcinoma (ESCC). But most patients end up with disease progression and/or therapeutic intolerance. The subsequent ICI rechallenge raises some discussions.