A 65-year-old woman was diagnosed with hepatocellular carcinoma (HCC) in February 20XX-1. Following three cycles of transarterial chemoembolization (TACE) for recurrent HCC, combination therapy with atezolizumab and bevacizumab (Atezo+Beva) was initiated in February Y, 20XX. Eight days after treatment initiation (Y+8), the patient developed a fever and generalized malaise. By day 14 (Y+14), her symptoms worsened, prompting a visit to her primary physician, where a fever of 39°C was recorded. However, no hypoxemia was observed, and she was sent home. The following day (Y+15), she developed dyspnea and hypoxemia (SpO2 in the 80% range), and chest computed tomography (CT) revealed a hilar central alveolar infiltration. She was subsequently admitted to her previous hospital. Comprehensive evaluation led to a diagnosis of congestive heart failure associated with thyrotoxicosis. According to the IMbrave150 study, thyroid dysfunction occurs in 13.4% of patients receiving Atezo+Beva therapy;however, cases classified as Common Terminology Criteria for Adverse Events Grade 3 or higher, requiring hospitalization, are extremely rare, with an incidence of only 0.3%.

Treatment of gestational trophoblastic disease (GTD) with chemotherapy is a success story for medical oncology; a combination of chemosensitive disease with a sensitive tumour marker makes GTD an eminently curable disease. However, 0·5-5·0% of women with this cancer continue to die as a result of multidrug resistance. PD-L1 is strongly expressed in these tumours, making them a target for immune therapy with immune checkpoint inhibitors such as pembrolizumab.

While new intrathoracic adenopathy in a patient with cancer can represent progression of disease, the differential diagnosis is broad. Sarcoid-like reactions (SLR) remain an underreported source of lymphadenopathy in patients treated with immune checkpoint inhibitors (ICI), with limited reports in patients with cancers other than melanoma.

Based on results of randomized clinical trials, polyADP-ribose polymerase inhibitors (PARPi) have become the standard of care in patients with platinum-sensitive recurrent ovarian cancer (OvC) in patients responding to platinum chemotherapy. However, little is known about their impact on survival in a real-world setting.

Malignant pleural effusion (MPE) is a severe complication in lung cancer, characterized by an immunosuppressive tumor microenvironment (TME) and limited therapeutic options. This study investigates the role of IL-6 in regulating immune suppression and tumor progression in MPE and evaluates the efficacy of dual IL-6 and PD-L1 blockade.

Immune checkpoint blockade (ICB) therapy has shown promising clinical efficacy in cancer treatment, but only a subset of patients experience significant therapeutic responses. Tumor cells respond to internal and external stresses, such as hypoxia and nutrient deprivation, by activating the unfolded protein response (UPR) in the tumor microenvironment. This response helps maintain homeostasis, promoting malignant progression, chemotherapy resistance, and immune escape. In this study, single-cell RNA sequencing (scRNA-seq) data from non-small cell lung cancer (NSCLC) patients treated with ICB revealed upregulation of thioredoxin (TXN) expression in the epithelial tissues of LUAD (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma) patients with minimal pathological remission. High TXN expression was also associated with "cold tumors," characterized by a lack of T cells and low levels of chemokine receptors and immunomodulators. Experimental results showed that TXN was highly expressed in NSCLC tissues, and its knockdown significantly inhibited the proliferation and migration of A549 and SK-MES-1 cells. Furthermore, TXN knockdown enhanced T-cell-mediated cytotoxicity against these tumor cells, suggesting that TXN contributes to immune escape in NSCLC by promoting tumor cell proliferation and migration while inhibiting immune killing. Notably, TXN knockdown also upregulated CD40 expression, indicating that TXN may regulate immune escape in lung cancer through CD40 modulation.

This study aimed to assess the effectiveness of combining selenium nanoparticles (SeNPs) with mitomycin C (MMC) in treating the T24 high-grade bladder cancer cell line to decrease MMC dosage and alleviate its side effects. The T24 (EJ138) cell line was exposed to various concentrations of SeNPs and MMC to identify the IC50 values via the MTT assay. The IC50 of MMC was then lowered by 25%, 50%, and 75%, and different SeNPs concentrations were added, to find the new IC50 values of these combinations. Apoptosis rates were measured using Annexin-V/PI staining, while the DNA cell cycle was analyzed using the PI staining method. The scratch-wound assay, colony-forming assay, and Hoechst staining were employed to examine the cell migration, proliferative capacity, and nuclear morphology, respectively. Real-time PCR assessed the expression levels of SNAIL, E-cadherin, and genes related to angiogenesis and proliferation (VEGF-C and HIF-1α), alongside the apoptosis markers (Bcl-2 and BAX). The co-administration of SeNPs and MMC (178.8 µM SeNPs + 14.9 µM MMC) significantly increased the rate of early apoptosis in the T24 cell line compared to MMC alone (29.8 µM, p < 0.0001). Additionally, SeNPs and MMC induced cell cycle arrest at the SubG1/G1 and G2/M phases, respectively. This effect was observed in the combination group at both phases. Similar to MMC alone, the combination group inhibited cell proliferation, colony formation, and migration in T24 cells (p > 0.05). Our findings indicate that the treatment with the combination increased the expression of apoptosis-related genes and decreased angiogenesis and proliferation-related gene expression similar to MMC alone (p > 0.05). The combined administration of MMC and SeNPs enhances the antitumor efficacy on the T24 cell line. It is proposed that the concurrent use of SeNPs and MMC could effectively reduce the required dosage of MMC, thus minimizing its negative side effects.

Surufatinib is a novel, China-developed small-molecule tyrosine kinase inhibitor that demonstrates high selectivity for VEGFR, FGFR1, and CSF1R. Surufatinib has been approved for the treatment of neuroendcrine tumors, including pancreatic neuroendocrine tumors (PNEN) and non-pancreatic neuroendocrine tumors (N-pNEN). The purpose of this retrospective study is to assess Surufatinib's safety and effectiveness in patients with various advanced solid malignancies. The general clinical statistics and follow-up data of patients treated with Surufatinib for advanced solid tumors at Zhejiang Provincial People's Hospital between January 2021 and April 2024 were gathered. Enhanced CT was used to assess the effectiveness during that time, and cases side effects were gathered. Survival rates of different diseases were analyzed using the Kaplan-Meier method. A total of 28 eligible patients were enrolled in this study. At the end of follow-up, treatment with Surufatinib resulted in the following outcomes: Complete response (CR) in 0 cases (0.0%), Partial response (PR) in 5 cases (17.9%), Stable disease (SD) in 7 cases (25.0%), and Progressive disease (PD) in 16 cases (57.1%). Objective response rate (ORR) and Disease control rate (DCR) were 17.9% and 42.9%, respectively. In the PNEN group, ORR was 33.3%, DCR was 66.7%, median progression-free survival (mPFS) was 11 months, while median overall survival (mOS) was 17 months. In the N-pNEN group, ORR was 14.3%, DCR was 42.3%, mPFS was 6 months and mOS was 7 months. ORR was 8.3%, DCR was 25%, mPFS was 2 months, and mOS was 2 months. The most common adverse reactions included hypoproteinemia, proteinuria, bone marrow suppression and gastrointestinal toxicity, and which of them were grade 1 to grade 2. In advanced solid tumors beyond PNEN, Surufatinib demonstrates clinically meaningful survival benefits for patients refractory to standard therapies, with a generally manageable safety profile.

Therapeutic drug monitoring (TDM) is used to optimize drug therapy by ensuring efficacy or preventing toxicity. For a limited number of cytotoxic antineoplastic drugs, for aminoglycoside antibiotics, and for vancomycin the use of TDM is common practice. In this article, we summarize recent advances and indications for the TDM of antineoplastic agents in children, focusing on protein kinase inhibitors and the cytotoxic drug fludarabine. We also summarize recent recommendations for antimicrobial TDM of beta-lactam antibiotics and vancomycin.

Pharmacogenomics remains underutilized in pediatric oncology, despite the existence of evidence-based guidelines. Implementation of pharmacogenomics-informed prescribing could improve medication safety and efficacy in pediatric oncology patients, who are at high risk of adverse drug reactions. This study examines the prevalence of high-risk pharmacogenomic phenotypes and the prescription of relevant medications in a diverse Australian pediatric oncology cohort, highlighting the potential impact of pharmacogenomic testing in this unique population. Whole genome sequencing data from 180 patients were analyzed to assess 14 genes with evidence-based pharmacogenomic guidelines relevant to pediatric oncology. Over 90% of patients had at least one high-risk phenotype, with 20% presenting four or more. Ondansetron, mercaptopurine, omeprazole, pantoprazole, and voriconazole were commonly prescribed medications that have pharmacogenomic prescribing recommendations, with the latter three showing the highest actionability rates. High-risk phenotypes were most frequently observed for CYP2C19 and CYP2D6, with 30% of patients having a high-risk phenotype for both genes. This study underscores the potential utility of pharmacogenomics in pediatric oncology patients across a range of pharmacogenes and commonly prescribed medications. The findings support advocacy for implementing broad, pre-emptive pharmacogenomic testing in oncology patients to improve treatment safety and efficacy.

This study examines the impact of continuous infusion chemotherapy via femoral artery catheterization on Golgi protein 73 (GP73) and alpha fetoprotein heterogeneity (AFP-L3) in liver cancer patients. A retrospective analysis was conducted on 108 liver cancer patients treated from January 2020 to December 2022, divided into two groups: transarterial chemoembolization (TACE) and continuous infusion regional arterial chemotherapy via femoral artery catheterization (CIFAC), with 54 patients in each group. Serum tumor markers, liver function, adverse reactions, quality of life, and 1-year survival rate were analyzed and compared between the two groups of patients. Prior to treatment, no significant differences were observed in tumor markers, liver function, and quality of life between groups (P > 0.05). After 60 and 90 days, the CIFAC group exhibited significantly lower levels of GP73, AFP, and AFP-L3 compared to TACE (P < 0.05). Additionally, CIFAC patients had lower levels of alanine aminotransferase (ALT), aspartate transaminase (AST), indocyanine green (ICG15) (P < 0.05), reduced adverse reactions (nausea, vomiting, etc.), and higher Karnofsky scores (P < 0.05). The one-year survival rate of the CIFAC group was significantly higher than that of the TACE group (P < 0.05). Continuous infusion chemotherapy through femoral artery catheterization can help reduce serum tumor marker levels, improve liver function, and reduce adverse reactions in liver cancer patients.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, primarily driven by KIT or PDGFRA mutations. Programmed cell death (PCD), including apoptosis, autophagy, and ferroptosis, plays a crucial role in GIST pathogenesis, progression, and treatment response. Non-coding RNAs (ncRNAs) have emerged as key regulators of PCD pathways, influencing GIST proliferation, metastasis, and drug resistance, particularly in response to tyrosine kinase inhibitors (TKIs) such as imatinib. Apoptosis suppression is strongly associated with poor prognosis, while autophagy contributes to tumor dormancy and TKI resistance. Ferroptosis, a novel iron-dependent cell death pathway, represents a promising therapeutic target. Recent evidence suggests that ncRNAs modulate these PCD pathways through interactions with key molecular regulators such as miR-494, miR-30a, and lncRNAs, which affect signaling networks including PI3K/AKT, MAPK, and mTOR. Furthermore, ncRNAs have mediated secondary resistance to imatinib by promoting autophagic flux and altering ferroptosis sensitivity. Understanding the molecular interplay between ncRNAs and PCD in GIST provides novel insights into disease mechanisms and offers potential therapeutic strategies to overcome drug resistance. Targeting ncRNA-mediated regulation of apoptosis, autophagy, and ferroptosis may enhance treatment efficacy and improve patient outcomes. Future research should focus on elucidating the mechanistic roles of ncRNAs in PCD pathways to develop innovative diagnostic and therapeutic approaches for GIST.

To measure the importance of factors that influence the decision to discontinue treatment due to chemotherapy-induced peripheral neuropathy (CIPN) among patients with metastatic breast cancer (mBC).

Acute myeloid leukemia (AML) is characterized by the malignant proliferation of abnormally or poorly differentiated myeloid cells in the hematopoietic system. However, there is a lack of effective drugs for treating non-M3 AML. V8, a newly synthesized derivative of the natural flavonoid wogonin, which is a potential anticancer drug, has demonstrated significant antitumor activity both in vitro and in vivo. Here, we investigated the effects of V8 on AML cell lines and primary AML cells as well as its underlying mechanisms. Our results showed that V8 exerted significant concentration-dependent growth inhibition and apoptosis induction in AML cells, accompanied by characteristic pathological features including lysosomal functions suppression, mitochondrial dysfunction, and endoplasmic reticulum stress (ERS) activation. Mechanistic investigations revealed that V8 induced mitochondrial membrane potential collapse through elevation of intracellular reactive oxygen species (ROS) levels, while concurrently blocking mitophagy via lysosomal functional inhibition. Furthermore, V8 selectively activated the PERK/p-eIF2α/ATF4 and IRE1α/XBP1 signaling axes of ERS, ultimately triggering CHOP-mediated apoptosis through the ERS-specific pathway. In vivo studies confirmed that V8 treatment significantly prolonged survival duration in NOD/SCID mice bearing primary AML xenografts and suppressed tumor progression in BALB/c nude mice with U937 cell xenografts, with antitumor efficacy closely associated with CHOP-dependent ERS pathway modulation. These findings not only elucidate the multi-targeted mechanism of V8 against AML through coordinated regulation of the ROS-mitochondria-lysosome-ERS signaling network, but also provide critical theoretical foundations for developing natural product-based therapeutics for AML. The multi-pathway synergistic characteristics exhibited by V8 underscore its considerable potential as a clinically translatable candidate drug.

Icaritin (ICT) shows great potential in cancer therapy. To enhance the cancer-fighting properties of icaritin against hepatocellular carcinoma (HCC), we developed icaritin-loaded liposomes modified with hyaluronic acid (HA-Lip-ICT). We employed statistical design methods to analyze how various factors affected particle dimensions and drug encapsulation, creating an optimized HA-Lip-ICT formulation that could effectively suppress HCC cell growth and trigger cellular aging. The human HCC cell line Huh7 was then exposed to different icaritin preparations. We assessed tumor cell viability through multiple assays, including colony formation and DNA synthesis measurements. Our results demonstrated that the refined HA-Lip-ICT significantly impaired HCC cell proliferation. Moreover, at a concentration of 10 μmol/L, HA-Lip-ICT markedly accelerated cellular senescence in HCC cells. These observations support our initial hypothesis that HA-Lip-ICT can inhibit HCC cell growth and promote their aging. While further research is needed to elucidate the exact mechanisms, this approach shows the promise of HA-Lip-ICT as a targeted therapy for improving the HCC treatments.

Aspirin's potential as a cancer treatment had garnered significant attention over the past 50 years. Presently, researchers are focused on structurally modifying aspirin to enhance its anticancer efficacy. In this study, aspirin was employed as the parent compound, and N-acylation of aspirin chloride with piperazine-sulfonamide hybrids was utilized to efficiently synthesize promising anticancer agents 3. Biological assays and structure-activity relationship analysis demonstrated that the incorporation of thiophene groups significantly enhanced the anticancer activity of aspirin. Among all eight human cancer cells treated, hybrid 3k, containing a bromothiophene structure, was the most effective against human non-small-cell lung cancer (A549) cells (IC50 = 36 μM), exhibiting over 33-fold greater toxicity than parent aspirin (IC50 > 1200 μM) and a higher selectivity index (SI = 6). Mechanistic studies revealed that hybrid 3k induced apoptosis in A549 cells and arrested the cell cycle at the G0/G1 phase. Molecular docking analysis and COX-2 inhibition assay indicated that hybrid 3k likely exerts its anticancer effects through the inhibition of COX-2 protein. These findings underscore the potential of hybrid 3k as a novel therapeutic agent for non-small-cell lung cancer and its contribution to expanding the antitumor scope of aspirin.

Carprofen, a nonsteroidal anti-inflammatory drug (NSAID) derived from propanoic acid, is known for its analgesic and antipyretic properties. Although it has long been employed in veterinary medicine as an anti-inflammatory agent, its use in humans was discontinued shortly after its market launch due to costly raw materials, complex synthesis, and labor-intensive production processes-factors that made it less competitive compared with other NSAIDs. Despite this, the carprofen molecule remains a subject of significant scientific interest. Recent advancements in its synthesis have introduced simplified and more cost-effective methods, reigniting its potential for both novel applications and drug repurposing. Exciting new research is exploring carprofen's broader therapeutic possibilities, extending beyond its original anti-inflammatory role. Studies are investigating its efficacy in antimicrobial therapy-including antibiofilm, anticancer, antiviral, and anti-Alzheimer's applications-opening doors to a wealth of untapped possibilities. This review delves into these emerging areas, highlighting how carprofen's molecular structure and derivatives can be leveraged to expand its therapeutic reach. The literature review was conducted using four databases: Web of Science, ScienceDirect, Scopus, Embase, and Reaxys. The review focused on English-language original research and review articles, examining carprofen and its derivatives in terms of their synthesis methods as well as their use as small molecules in various therapeutic applications, both human and veterinary. With ongoing research pushing the boundaries of its potential, carprofen remains a promising candidate for innovation in drug development and treatment strategies.

This research aims to elucidate the mechanistic role of artesunate (ART) in enhancing the sensitivity of renal cell carcinoma (RCC) to sunitinib. To establish sunitinib-resistant RCC cell lines (786-O R and Caki-1 R), cells were treated with different concentrations of sunitinib and ART. The viability of the cells was measured through the cell counting kit-8 (CCK-8) assay. Tripartite motif-containing 24 (TRIM24) and paired box 6 (PAX6) expression were suppressed with lentiviral vectors, quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) analysis. TRIM24-PAX6 interaction was examined through co-immunoprecipitation (Co-IP) and deubiquitination assays. Additional assays included colony formation, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, WB detection of phosphorylated histone H2AX (γ-H2AX) for DNA damage, epithelial-mesenchymal transition (EMT) marker analysis, sphere formation, and stemness marker assessments. In vivo drug resistance was tested using a mouse subcutaneous xenograft model. ART enhanced sunitinib sensitivity in resistant RCC cells, reducing colony formation, inducing apoptosis, elevating γ-H2AX, and upregulating TRIM24. ART enhances sunitinib sensitivity in RCC cells by upregulating TRIM24 expression, which facilitates the ubiquitination of PAX6. This process leads to the suppression of EMT and stem cell-like transitions in RCC cells.

Solanum lycopersicum L. Moench (Tomato) is a rich source of bioactive compounds. This study investigated the anticancer potential of S. lycopersicum roots methanol extract (TMESLR) and their nanocrystals (TMESLR-NCs) against breast (MCF-7), hepatocellular (HepG2), and colon (Caco-2) cancer cell lines, for the first time. TMESLR exhibited significant cytotoxicity against all 3 cell lines, with the nanocrystals demonstrating enhanced activity, Caco-2, MCF-7, and HepG2 cells with IC50 values of 9.69 ± 0.6, 12.52 ± 0.58, and 14.34 ± 0.62 µg/mL, respectively. Whereas, the prepared TMESLR-NCs displayed significantly the highest cytostatic potential against Caco-2 with IC50 value of 5.733 ± 0.29 µg/mL. Metabolomic profiling revealed 17 secondary metabolites, including flavonoids, phenolic acids, and terpenoids. In silico analyses, including PPI network construction, GO enrichment, and KEGG pathway analysis, highlighted the involvement of apoptotic pathways, p53 signaling, and TNF signaling in the anticancer effects of TMESLR. Molecular docking studies identified chlorogenic acid and inosine as potential inhibitors of Histone Deacetylase 2 (HDAC2). Inosine (6) displayed a superior docking score of -7.86 kcal/mol, interacting with critical residues GLY154, ASP269, and HIS146. On the other hand, chlorogenic acid (12) achieved a docking score of -7.32 kcal/mol, forming stable interactions with TYR308, PHE210, and LEU276 residues. These findings suggest that TMESLR and TMESLR-NCs possess promising anticancer activity and warrant further investigation as potential therapeutic agents.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with poor survival rates in adults, posing a significant economic burden. FMS-like tyrosine kinase 3 (FLT3) mutations are linked to poor prognosis in AML and resistance to clinically approved FLT3 inhibitors. Previously, we reported a novel benzimidazole-based FLT3 inhibitor, 4ACP, with nanomolar activities against FLT3-ITD and FLT3-TKD mutants, showing selective cytotoxicity against FLT3-ITD+ AML cell lines. In this study, we synthesized 31 derivatives by modifying the 4-acetamidophenyl group and varying substituents at N1-phenyl and C2 positions. We identified compound 21l (3-acetamidophenyl) as the most potent derivative (FLT3-TKD(D835Y) IC50 = 1.47 nM). Linking 21l to a solvent-accessible group yielded compound 22b, which exhibited a sub-nanomolar activity against FLT-TKD(D835Y) mutant with an IC50 value of 0.48 nM. Compound 22b showed preferential antiproliferative activities against MOLM-14, MV4-11, MOLM-14-D835Y, and MOLM-14-F691L AML cell lines with IC50 values of 16.1, 10.5, 26.5, and 160.3 nM, respectively. 22b induced dose-dependent inhibition of FLT3, ERK, STAT5, and S6 phosphorylation, G0/G1 cell-cycle arrest, and apoptotic cell death at low nanomolar concentrations in MOLM-14 and MOLM-14-D835Y cells. It was more selective for FLT3-dependent cell lines, showing about 80-fold selectivity toward FLT3-TKD(D835Y) over KIT, indicating relative safety and lower myelosuppression potential. The molecular dynamics study of 4ACP and 22b was conducted to explain the significant changes in activity resulting from subtle structural alterations. Altogether, these findings establish 22b as a potent mutant FLT3 inhibitor, warranting further investigation and optimization to target resistant AML.