Immune checkpoint inhibitor (ICI) have demonstrated efficacy in treating various cancers by modulating the immune system, but this can lead to immune-related adverse events (irAEs), including myocarditis. ICI-associated myocarditis is a rare but highly lethal irAE with a short mean time to onset, and difficult to diagnose early due to nonspecific symptoms and lack of biomarkers. This review highlights the need for improved recognition and management of ICI-associated myocarditis, summarizing recent advances in immunology, pathology, and biomarker research. We discuss the epidemiology, clinical features, immunological mechanisms, and roles of biomarkers in diagnosis and risk stratification. Traditional biomarkers like cTnI and hs-cTnT are sensitive but lack specificity, while emerging biomarkers like miR-155 show tissue specificity. Inflammatory markers such as NLR and CRP aid prognosis but have limited diagnostic value.

Glioblastoma is the most predominant type of brain tumor, and resistance to medication has hampered the effectiveness of chemotherapy for gliomas. Acyclic monoterpene alcohol, linalool, has a range of pharmacological properties. The present study aimed to evaluate the impact of linalool and its nanoformulation on glioblastoma cell proliferation. DFT and ADMET analyses were used to initially assess the physiochemical characteristics of linalool and the produced silver nanoconjugates, LN@AgNPs. STRING database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to narrow the 6 genes involved in glioblastoma and underwent for molecular docking study. Using AutoDock Vina 1.5.7, ligands were docked to the interaction site of selected targets. Top scored complexes PD-L1/Ligands and PTEN/ligands were simulated using molecular dynamics. The results revealed that LN@AgNPs produced a more stable complex, because metallic bonds are more robust and durable than hydrogen bonds, which give metals their distinctive strength and stability. To confirm the cytotoxicity of the compound against GBM cell line SF-767, linalool and LN@AgNPs were evaluated by in vitro study to check the expression at the IC50 concentration of top scored selected genes. The results indicated that the cytotoxic effects of linalool and LN@AgNPs were concentration dependent. In the SF-767 cancer cell line, linalool and LN@AgNPs with IC50 (33.14 µg/mL and 22.12 µg/mL respectively) values downregulated PD-L1 expression and increased PTEN expression. In conclusion phytocompounds conjugated with AgNPs increased cytotoxicity and inhibition index in glioblastoma cells. Therefore, LN@AgNPs may be a viable option for cancer treatment.

Nigella sativa L. widely used spice cum medicinal plant in Asia and the middle east, is renowned for its seeds and oil which possess both culinary and therapeutic purposes. Its rich content of bioactive compounds, including metabolites and phenolics, with Thymoquinone, a monoterpene quinone, emerging as key therapeutic compound significantly consideration for its various pharmacological activity with lower toxicity compared to conventional chemotherapy. This study evaluated the anticancer potential of thymoquinone isolated from N. sativa L., through cytotoxicity and In Silico studies. Seeds from 38 accessions were collected across the country and screened for Thymoquinone content using HPTLC with the highest concentration identified in Ajmer Nigella 13 (247.60mg 100gm-1) accession. In Vitro MTT assay of Thymoquinone in human myelogenous leukemia (K562) cells demonstrated significant dose and time dependent cytotoxicity confirming Thymoquinone's potential as a promising therapeutic candidate for leukemia and other cancer.

Narrow therapeutic indices of chemotherapeutic agents necessitate precise dosing to ensure efficacy and minimize nephrotoxicity. Due to the complexity of directly measuring Glomerular filtration rate (GFR), renal dosing is usually based on GFR estimation equations. The Cockcroft-Gault formula remains the most widely used equation in cancer patients, despite the availability of more precise kidney function estimation equations. Therefore, the aim of the study was to assess the agreement between Cr and cystatin-C (CysC) based GFR estimation equations and GFR estimated by Cockcroft-Gault for appropriate chemotherapy dosing in cancer patients undergoing assessment for first-Line chemotherapy at an oncology unit of St. Paul's Hospital Millennium Medical College in Ethiopia.

IntroductionThe Cancer and Aging Research Group (CARG) model predicts chemotherapy-related toxicities in older patients; however, its applicability has not been validated in Taiwanese patients. This study aims to validate the CARG model in older Taiwanese patients with solid tumors.MethodsPatients (N = 258) aged ≥65 years with solid tumors from a single medical center, slated for first-line chemotherapy, were recruited between 2018 and 2021, with follow-up until December 31, 2022. Patients were categorized into low- (N = 85), medium- (N = 117), and high- (N = 56) risk based on CARG. Validation of CARG involved receiver operating characteristic (ROC) curves. Individual CARG variables were analyzed using univariate analysis for their impact on toxicities and survival.ResultsToxicities of grades ≥3 were 38.8%, 44.4%, and 67.9% (P = .001) in the three ascending risk groups, and there were significant differences in both hematological (P = .002) and non-hematological (P < .001) toxicities. ROC was 0.631 (95% CI: 0.562-0.700), indicating satisfactory discrimination. One-year overall survival rates were 88.7%, 79.7%, and 63.8%, respectively, in ascending-risk groups, with high-risk groups showing decreased survival (P = .002). In the multivariate analysis, decreased hemoglobin, history of falls, and inability to walk one block remained significantly associated with toxicity. For overall survival, the inability to take medications was the only independent predictor.ConclusionThis prognostic study validated the CARG model in a heterogeneous solid tumor cohort in Taiwan. In addition to predicting both hematological and non-hematological toxicities, CARG could offer insights into patient survival among older individuals with cancer.

Hepatocellular carcinoma (HCC) remains a major global health challenge, with limited efficacy of current immunotherapeutic strategies. Immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns (DAMPs), offers a promising approach to enhance antitumor immunity. Arsenic trioxide (ATO), an ICD inducer, may synergize with PD-1 inhibitors to overcome therapeutic resistance, though the underlying mechanisms remain unclear.

Diarrhea is primary adverse effect of capecitabine (Cap) causing treatment discontinuation. The aim of this study was to construct an early-warning model for predicting the Cap-induced diarrhea.

Dauriporphine is a major ingredient of Manispernum daericum DC., which has been demonstrated to show wide anti-tumor activities. miR-424-5p, as a regulator of lung cancer, was hypothesized to serve as the therapeutic target for dauriporphine This study evaluated the potential of dauriporphine in treating lung adenocarcinoma and revealed the underlying molecular mechanism.

Regarding their distinct physico-chemical and bioactivity characteristics, silver nanoparticles 'AgNPs' are extensively utilized in numerous scientific purposes.

Glioma is a highly aggressive central nervous system tumor with limited treatment options, presenting a significant challenge for effective therapy. Despite advancements, the role of tumor-associated macrophages (TAMs) in glioma remains poorly understood, especially regarding their polarization and its impact on the immune response. This study investigates the effects of Lysosomal-associated protein transmembrane 4 A (LAPTM4A) deficiency on the polarization of TAMs and its role in modulating anti-tumor immunity. Using C57BL/6 male mice, we established an orthotopic glioma model and employed single-cell RNA sequencing, flow cytometry, in vitro co-culture systems, and in vivo anti-PD-1 therapy experiments to explore the functional role of LAPTM4A. We found that LAPTM4A promotes M2 polarization of TAMs, contributing to glioma progression by enhancing cell proliferation and invasion. In contrast, LAPTM4A-deficient glioma models show a shift towards M1 macrophage phenotypes, leading to stronger immune activation and increased sensitivity to anti-PD-1 therapy. These results suggest that targeting LAPTM4A may provide a novel strategy to improve glioma treatment by modulating TAM polarization and enhancing immune responses. This research lays the groundwork for future therapies aimed at reprogramming the tumor microenvironment to combat glioblastoma.

Imatinib treatment is approved for several indications, including chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). Although adverse events are common, hypersensitivity reactions are not. Because there is a clear clinical benefit of imatinib treatment, re-introduction of imatinib after a hypersensitivity reaction should be considered.

A series of aminated quinolinequinones linked to piperazine analogs (QQ1-7) were synthesized and screened against the full panel of National Cancer Institute (NCI) cancer cell lines for their potential as cytotoxic agents. The Developmental Therapeutics Program of the NCI analyzed the NCI-60 screening results and revealed that seven QQs were potent inhibitors of cancer cell growth across several cell lines, advancing them to the five-dose assay. Encouraged by the NCI five-dose assay results, the cytotoxicity of the selected QQs (QQ1 and QQ4) was further studied in three cancer cell lines-HCT-116 (colon cancer), ACHN (renal cancer), MCF7, and T-47D (breast cancer)-as well as in a normal cell line (HUVEC) for a deeper understanding. QQ1 was the hit compound for ACHN cells with an IC50 value of 1.55 μM. QQ1 could inhibit ACHN cell proliferation, induce oxidative stress, and cause cell cycle arrest in ACHN cells. QQ1 did not affect the apoptotic value in ACHN cells. Oral bioavailability was poor for both QQ1 and QQ4 in vivo in rats due to faster intrinsic hepatic clearance in comparison with humans, as evidenced by in vitro metabolic studies with rat and human liver microsomes. Molecular docking simulation with putative target CDC25A revealed the interaction of QQ1 and QQ4 with active site residues responsible for substrate recognition.

Tumorigenesis and metastasis of solid tumors are coupled to profound biophysical changes that alter cancer cells' mechanobiology, critically impacting metastatic progression. In particular, cell stiffness determines the ability of cancer cells to invade surrounding tissues, withstand shear fluid stress and evade immune surveillance. Here, we summarize the biological factors, pathological factors, and therapeutic modalities that affect the mechanobiology of cancer cells. We focus on clinically utilized chemotherapeutics and targeted therapies that show direct and indirect modulation of cancer cells' stiffness and discuss how these treatments can be used in combination with other treatment modalities to improve patient outcomes. Finally, we list the outstanding challenges in the field and provide a perspective on expanding the clinical utilization of experimental therapeutics that can act as "mechanotherapeutics" by regulating mechanobiology of cancer cells.

Besides targeting tumor cells via canonical synthetic lethality, poly(ADP-ribose) polymerase inhibitors (PARPis) can remodel tumor immune microenvironment (TIME), which then affects PARPis' anti-tumor capabilities. However, exact function of PARPis on TIME remains insufficiently explored. Here, by leveraging paired samples during neoadjuvant PARPi Niraparib treatment derived from a prospective clinical trial, we discovered that the expression of immune checkpoint ligand B7-H3 was induced by PARPis in cancer-associated fibroblasts (CAFs) of ovarian cancer. Depletion of B7-H3 in CAFs by using host cd276 (coding B7-H3) knockout mice or B7-H3 deficient fibroblast cells both boosted T cell functions and enhanced the anti-tumor capacities of PARPis in immunocompetent mouse models. Besides, increased B7-H3 on CAFs also attenuated the anti-tumor potentials of T cells in co-culture system. Mechanistically, PARPis blocked autophagic flux by inhibiting PIP4K2A expression, a critical regulator of autophagosome and lysosome fusion, and therefore dampening the lysosomal degradation of B7-H3. Importantly, neutralizing B7-H3 antibodies had synergistic effects with PARPis and achieved superior therapeutic efficacy than PARPis plus PD-1 blockade in a syngeneic mouse ovarian cancer model. Collectively, this study revealed an autophagy-mediated pathway by which PARPis contribute to immune evasion via enhanced B7-H3 accumulation on CAFs, highlighting the complexity of the regulation of PARPis on TIME and the potential application of combining PARPis with B7-H3 blockade in the treatment of ovarian cancer.

Thymic epithelial tumors (TETs), categorized predominantly as thymoma (T) or thymic carcinoma (TC), face a challenging prognosis and limited treatment options. Although chemotherapy remains the established treatment for advanced TETs, its responses tend to be short-lived. The emergence of immunotherapy, particularly programmed cell death-1 (PD-1) and programmed death ligand-1 inhibitors (PD-L1), is increasingly being regarded as a promising new treatment option for various malignancies.

As a member of the chaperonin-containing tailless complex polypeptide 1 (TCP1) complex, which plays a pivotal role in ensuring the accurate folding of numerous proteins, chaperonin-containing TCP1 subunit 6A (CCT6A) participates in various physiological and pathological processes. However, its effects on cell death and cancer therapy and the underlying mechanisms need further exploration in colorectal cancer (CRC) cells.

The Wnt/β-catenin signaling pathway is a highly conserved signaling pathway closely linked to cancer development through various biological processes, including oncogenic transformation, genomic instability, cancer cell proliferation, stemness, metabolism, cell death, immune regulation, and metastasis. Notably, its activation plays a crucial role in drug resistance to chemotherapy, targeted therapy and immunotherapy. Recent advances in drug development have identified several targeted inhibitors acting at key nodal points of this pathway, with some demonstrating synergistic efficacy when combined with immunotherapeutic agents. This review provides a comprehensive analysis of current understanding regarding the Wnt/β-catenin pathway in malignancy, emphasizing its multifaceted roles in tumor initiation, therapeutic resistance, and immune regulation. Additionally, we summarized the clinical performance of combination therapies targeting the Wnt/β-catenin pathway in conjunction with chemotherapy, targeted therapy, and immunotherapy. Although clinical development remains at a relatively early stage, pharmacological modulation of Wnt/β-catenin signaling offers considerable potential as a novel therapeutic paradigm in precision oncology.

Extracellular vesicles (EVs) play a crucial role in intercellular communication. While the effects of EVs released from living or non-dying cancer cells are well characterized, the impact of EVs released from chemotherapy-treated or apoptotic cancer cells is less understood. This study investigated the effects of the chemotherapy agent cisplatin on EV release and miRNA content in apoptotic medulloblastoma cells, as well as their influence on the growth of drug-naïve recipient cancer cells.

The complex dual role of autophagy provides new insights for enhancing tumor treatment efficacy. However, effectively regulating this process is key to enhancing therapeutic efficacy. To address this challenge, this study designed a gambogic acid-iron nanozyme (GAFe) as a novel carrier to enhance the effectiveness of chemotherapy drugs such as doxorubicin (DOX) by inducing excessive autophagy and oxidative stress. The synthesized nanoparticle (GAFe@DOX) is capable of slowly releasing its active components over a prolonged period within tumor tissues. Gambogic acid can induce excessive autophagy, while the multi-enzyme activity of GAFe and the activation of ferroptosis amplify and sustain excessive autophagy, thereby enhancing the chemotherapy effect of DOX. Meanwhile, ferroptosis activated via the GPX4 pathway by GAFe can synergize with excessive autophagy, amplifying oxidative stress and consequently enhancing the overall therapeutic efficacy. Characterization experiments confirmed the successful synthesis of GAFe@DOX and probe assays demonstrated its superior multi-enzyme activity. In vitro cell studies showed that GAFe@DOX effectively kills tumor cells, while in vivo animal experiments revealed its excellent biocompatibility and significant tumor growth inhibition. This study demonstrates a promising strategy to improve tumor therapeutic efficacy by modulating excessive autophagy and oxidative stress. This provides a novel and effective approach to improve the treatment of refractory tumors such as glioblastoma.

Immune checkpoint inhibitors (ICIs) plus chemotherapy have become the first-line standard therapy for non-oncogene addicted advanced non-small cell lung cancer (NSCLC) patients. There is a lack of reliable biomarkers to predict treatment outcomes. This study aimed to identify relevant lipids that can predict treatment outcomes in NSCLC patients receiving first-line ICIs plus chemotherapy via lipidomics.