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.

Currently, given variations in the abnormal tumor microenvironment (TME), significant progress has been made in the treatment of breast cancer (BC) based on TME-responsive nanosystems-mediated ferroptosis. Due to inherent deficiencies such as the limited efficacy of Fe-induced catalysis, the lack of endogenous hydrogen peroxide (H2O2), and the overexpression of glutathione (GSH) in tumor cells, the treatment of ferroptosis is restricted. Here, this document highlighted polymeric nanoparticles with GSH resection (ssP-tHB@Fe/DOX), demonstrating significant improvements in TME responses, biocompatibility, and anti-tumor effects. Our study offers a platform for combined BC amplification therapy involving ferroptosis and DOX-induced chemotherapy, and it highlights the use of 3,4,5-trihydroxybenzaldehyde (tHB) in a Fe(III)-Fe(II) cyclic reaction to deplete GSH and enhance ferroptosis. Notably, ssP-tHB@Fe/DOX could effectively disrupt mitochondrial structure and reduce membrane potential in tumor cells, leading to decreased ATP production, depletion of GSH via multi-channel approach, inhibition of GPX4 expression, and accumulation of lipid peroxidation, thereby inducing ferroptosis enhancement to achieve BC therapy. Meanwhile, the release of the anticancer drug DOX has dual effects: it interferes with NADPH to enhance the Fe-mediated Fenton reaction and induces apoptosis in tumor cells. Moreover, RNA sequencing (RNA-seq) analysis robustly supported the anti-tumor mechanism of ssP-tHB@Fe/DOX, confirming involvement in the amino acid metabolism ferroptosis signaling pathway and the p53 signaling pathway, etc. Therefore, in this study, we thoroughly introduced the design of intelligent nanosystems, proposed methods to enhance DOX-induced apoptosis and ferroptosis, offering a novel approach for cancer treatment.

Von Hippel-Lindau (VHL) syndrome is an autosomal dominant hereditary disease characterized with mutiple organ tumors. Tyrosine kinase inhibitor (TKI) is one of the targetd treatment for VHL syndrome. Lenvatinib (LEN), an oral small-molecule multiple TKI, and proteinuria is one of the most common adverse events associated with LEN. We reported a case of lenvatinib-induced nephrotic syndrome in a Chinese patient with VHL syndrome. The renal biopsy was proved with thrombotic microangiopathy (TMA) and focal segmental glomerulosclerosis (FSGS)-like pattern. Drug-induced kidney injury deserves further attention.

Breast cancer remains a leading cause of cancer-related mortality in women worldwide. Hypericin (HYP) is a natural photosensitizer and hypericin-mediated photodynamic therapy (HYP-PDT) has shown promise in cancer treatment. PARP inhibitors like Olaparib are effective in BRCA1-mutant breast cancers but have limited efficacy in BRCA1 wild-type breast cancer. This study investigated the synergistic antitumor effects of HYP-PDT combined with Olaparib in BRCA1 wild-type breast cancer cells. MCF-7 cell line, a well-characterized and commonly utilized model for BRCA1 wild-type breast cancer was employed in this study. We evaluated the cellular responses to varying concentrations of HYP and Olaparib followed by PDT, through assessments of reactive oxygen species (ROS) production, DNA damage signaling pathways, apoptosis, cell cycle distribution, and migration capabilities. Results demonstrated that both HYP-PDT and Olaparib individually inhibited cell proliferation in a dose-dependent manner, with their combination synergistically enhancing antitumor efficacy. HYP-PDT induced intracellular ROS generation and DNA damage, which were further amplified by Olaparib. The combination treatment modulated the ATM/p53/RAD51 signaling pathway, leading to apoptosis and G2/M phase cell cycle arrest through the regulation of mitochondrial apoptosis-associated proteins and cell cycle checkpoint proteins. Furthermore, the combination treatment inhibited epithelial-to-mesenchymal transition (EMT), thereby reducing MCF-7 cell migratory capability. These findings highlight the potential of combining HYP-PDT with Olaparib as a promising strategy to overcome the limitations of monotherapies and provide a novel approach for treating BRCA1 wild-type breast cancer.

OM is a very relevant and sometimes therapy-limiting side effect of CT/RCT. There are prophylactic and therapeutic measures available that should be recommended to all patients. This study investigated how patients were informed about oral mucositis (OM) as possible side effect of CT/RCT, how well they knew about available prophylactic and therapeutic measures from the clinical guidelines and to what extent they applied these.

The plant kingdom is a crucial source of potential medicines, with medicinal plants playing a significant role, they have been used to treat various diseases, including cancer. Phytochemicals have emerged as promising candidates for enhancing conventional cancer treatment strategies, particularly in addressing the persistent challenges associated with such therapies. For a long time, combined therapy has been widely adopted to overcome the limitations of monotherapies. To optimize therapeutic outcomes, it is crucial to understand the mechanisms underlying the interactions between phytochemicals and conventional drugs. Based on the above, we have developed a database named InterPAD, which serves as a valuable resource to retrieve detailed information on the interactions between phytochemicals and anticancer drugs. It offers insights into their mechanisms of action and therapeutic effects, thereby facilitating a deeper understanding of how these phytochemicals can be effectively integrated into modern cancer treatment protocols. A total of 1,055 interactions involving 331 phytochemicals and 244 anticancer drugs were meticulously reviewed and manually curated from the original publications into the InterPAD database. Additionally, InterPAD curates from 680 medicinal plants, providing detailed phytochemicals-related plant information. The database also includes 619 regulatory molecules and 74 cancer types, sourced from other databases, to elucidate cancer-specific molecular mechanism and therapeutic effects. To our knowledge, InterPAD is the first comprehensive database to investigate the synergistic or antagonistic interactions of phytochemicals with drugs across various cancer types. It uniquely highlights the biological effects of phytochemicals-based anticancer interactions through the framework of "multiple-regulatory molecules and multiple-signaling pathways", providing insights into their molecular mechanisms. This resource serves as a valuable tool for advancing research and improving cancer treatment strategies. InterPAD is accessible at: https://bddg.hznu.edu.cn/interpad/ .

Prostate cancer (PCa), a common urinary malignancy, is the leading cause of mortality and morbidity among men worldwide. Curcuma amada extract has demonstrated antitumor properties in preclinical models of various cancers, however, its mechanisms against prostate cancer remain unclear. The current study aims to investigate the underlying mechanism of C. amada rhizome extract (CARE) in treating PCa through network pharmacology, bioinformatics analysis and in-vitro experiments. UHPLC-QTOF-HRMS/MS detected 16 phytoconstituents in C. amada, with 15 constituents passing drug-likeness criteria. Public databases identified 1,311 CARE and 473 PCa related targets, with 59 overlapping targets. PPI analysis revealed P53, CTNNB1, EGFR, AKT1, ESR1, HIF1A, CCND1, PIK3CA, and BCL2 as hub targets. Further,4-hydroxycinnamic acid, 13-hydroxylabda-8(17),14-dien-18-oic acid, labda-8(17),12-diene-15,16-dial, zederone, zedoarondiol, zerumin A and caffeic acid were identified as core compounds with high degree values. GO and KEGG analysis identified targets primarily associated with apoptosis and PI3K-AKT signalling pathway. Molecular docking confirmed good binding potential of core compounds with key hub targets, while molecular dynamics (MD) simulation validated the stability of these interactions with minimal fluctuations throughout the simulation. Additionally, mRNA expression levels, immune infiltration and genetic alteration of the hub targets were analyzed. CARE significantly inhibited the proliferation of PC-3 cells, induced apoptosis, and caused G2/M phase arrest. In addition, qRT-PCR analysis revealed that CARE was able to suppress mRNA expression of genes involved in the PI3K-AKT signalling pathway. Thus, the study highlights the underlying mechanism of CARE as a promising treatment option for prostate cancer.

Nanocrystals have great potential as improved drug carriers due to their low cost, high biodegradability, and biocompatibility. Thus, cellulose nanocrystals (CNCs) are particularly suitable for enhanced antibacterial and anticancer therapy. In this research, we report the green synthesis of β-cyclodextrin-functionalized cellulose nanocrystals (β-CD/CNCs) from pistachio shells as a carrier material for propolis, as well as the determination of its antibacterial and anticancer properties. The β-CD/CNCs were characterized using Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). FTIR analyses indicated the successful attachment of β-cyclodextrin to the cellulose nanocrystals. FE-SEM and TEM images of β-CD/CNCs exhibited rod-shaped morphology, while the XRD pattern revealed the crystal structure of β-CD/CNCs. The chemical composition of the propolis extract was investigated using GC-MS analysis. The incorporation of the propolis extract into the β-CD/CNCs was achieved with 10% encapsulation using the differential weighing method. Subsequently, the antibacterial and anticancer properties of the propolis-loaded β-CD/CNCs were determined. The antibacterial activity was assessed using the disk diffusion method (Kirby-Bauer method) and minimum inhibitory concentration (MIC) determination by the dilution method (DM). The anticancer properties were evaluated using MTT and flow cytometry assays on two liver cell lines (HepG2 and L929). The results demonstrated that the propolis loaded in β-CD/CNCs exhibited better antibacterial and anticancer activity than free propolis. Therefore, β-CD/CNCs can be suggested as a suitable carrier for propolis.

The use of immune checkpoint inhibitors (ICIs) is increasingly important in melanoma management. While ICIs are associated with immune-related adverse events (irAEs), little is known about skeleton irAEs and they are felt to be poorly described.

Immune checkpoint inhibitors targeting negative regulatory checkpoints including programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 have produced significant improvements in progression-free survival (PFS) and overall survival in multiple solid tumors. Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that is highly expressed by exhausted T cells. Dual blockade of LAG-3 and PD-1 with monoclonal antibodies relatlimab and nivolumab has improved PFS in advanced melanoma, leading to Food and Drug Administration approval for this indication. Concurrently, enthusiasm for targeting LAG-3 has been tempered by negative results in multiple indications, although novel approaches including LAG-3-directed bispecifics tebotelimab continue to demonstrate promise. In this review, we discuss the current understanding of LAG-3 in regulating antitumor immunity and the ongoing state of clinical development of LAG-3-directed agents in cancer.

To identify predictive gene-expression signatures for immune-related adverse events (irAEs) in patients with melanoma treated with anti-PD-1 inhibitors, in the adjuvant therapy (AT) and first-line therapy (FLT).

With the rapid introduction of novel breast cancer therapies, recognizing and managing side effects is essential to maintain adherence and improve outcomes. As novel oral endocrine therapies and combination strategies including targeted agents have prolonged progression and in some cases disease-free survival, early recognition and appropriate management of these toxicities is critical to optimize quality of life. Dermatologic adverse events are frequently associated with novel breast cancer therapies including immune checkpoint inhibitors (ICIs), targeted therapies, and antibody-drug conjugates (ADCs). These include various rashes, stomatitis, and alopecia, necessitating multidisciplinary dermatologic intervention to allow for prompt management of cutaneous toxicities and continuation of oncologic therapy. Targeted breast cancer therapies, including ADCs, can also induce ocular adverse events (OAEs), such as corneal pseudomicrocysts which lead to blurry vision and eye pain. Current preventative therapies have had limited success for these OAEs, necessitating dose interruptions. Although anthracycline-based chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy are associated with an increased risk of heart failure and left ventricular (LV) dysfunction, novel breast cancer therapies including ADCs, HER2 tyrosine kinase inhibitors, cyclin-dependent kinase 4 and 6 inhibitors, ICIs, and oral selective estrogen receptor degrader are also associated with an increased risk of LV dysfunction, heart failure, corrected QT prolongation, myocarditis, and bradycardia. This review provides a comprehensive overview of novel and emerging breast cancer therapy toxicities, with suggested management strategies to prevent and mitigate these adverse events. Through a multidisciplinary approach involving preventative strategies, monitoring, proactive interventions, providers can minimize symptom burden and improve patient adherence, ultimately improving breast cancer outcomes.

Cisplatin is widely used as a first-line chemotherapy drug for various cancers. However, cisplatin-induced nephrotoxicity (CIN) greatly restricts its application. Renal proximal tubular epithelial cells (RPTECs) can be extensively damaged during CIN. However, it still lacks an ideal method to prevent CIN, because the mechanism and therapeutic targets of CIN remain largely unclear. In the present study, we used a genome-scale CRISPR-Cas9 knock-out method to functionally screen key genes of cisplatin-induced RPTEC injury. We found 815 genes significantly enriched (p < 0.05) from positive selection screening strategy, which may synergistically enhance cisplatin cytotoxicity in RPTECs. Importantly, we identified ERAP2 as a novel molecule associated with CIN. We found that the expression of ERAP2 in RPTECs was significantly up-regulated by cisplatin. Data from CCK-8 assay and flow cytometry showed that inhibition of ERAP2 alleviated cisplatin-induced RPTEC injury. Furthermore, RNA-seq and qPCR results revealed that three necroptosis-associated genes, PLA2G4C, HIST1H2AC, and HIST1H2AM, were downregulated following ERAP2 inhibition, suggesting that ERAP2 may be a novel therapeutic target of CIN through the modulation of necroptosis pathway.

Neuroblastoma (NB), a common pediatric cancer, is often associated with poor prognosis due to resistance to conventional therapies. Abemaciclib, a selective inhibitor of CDK4/6, is known for its ability to block cell cycle progression and induce cell death in various cancer types. In this study, we explore its potential therapeutic impact on NB by assessing its effects on cell proliferation, apoptosis, and the regulation of microRNAs (miRNAs) that are related to NB progression. Antiproliferative effect of abemaciclib, doxorubicin, cisplatin, and temozolomide (TMZ) were detected by MTT method. Combinations of abemaciclib-doxorubicin, abemaciclib-cisplatin, and abemaciclib-TMZ were also investigated by applying IC50 doses of the drugs for 24 h. ELISA and flow cytometry were performed for apoptosis detection, and for cell cycle analysis, flow cytometry was used. The expression levels of eight apoptosis, threee tumor suppressors, two oncogenes, and nine cell cycle-related genes were analyzed by quantitative PCR. Moreover, the expression levels of five NB-related miRNAs were determined. IC50 doses of abemaciclib, doxorubicin, cisplatin, and TMZ were found to be 4.757, 1.958, 34.21, and 240.7 uM in the 24 h, respectively. The combination of the drugs increased apoptosis and decreased cell migration and colony formation rates. The highest expression level difference was observed in PUMA when control and dose groups were compared. Increased expression levels of hsa-mir-18a-5p and hsa-miR-124-3p were detected in all drug-treated groups compared to the control group. Our results highlight the potential of abemaciclib as a promising treatment strategy for NB, particularly when used in combination with other therapies to overcome resistance and improve clinical outcomes.