Anti-cancer Drugs[JOURNAL]
Sun
200 papers
Combined amlexanox and anti-MCP-1 therapy suppresses tumor progression in a murine Lewis lung carcinoma model.
Liu X, Dong X, Wei J … +3 more , Tian J, Han Y, Li H
Anticancer Drugs · 2025 Oct · PMID 40626452 · Publisher ↗
This study aims to assess the effects of combined amlexanox and an antimonocyte chemoattractant protein-1 (MCP-1) mAb therapy in a murine Lewis lung carcinoma (LLC) model. A subcutaneous LLC model was established in mice...
This study aims to assess the effects of combined amlexanox and an antimonocyte chemoattractant protein-1 (MCP-1) mAb therapy in a murine Lewis lung carcinoma (LLC) model. A subcutaneous LLC model was established in mice, which were allocated to either a control group or an intervention group receiving combined amlexanox and anti-MCP-1 mAb. Tumor size was monitored regularly. Immunofluorescence staining was performed to detect MCP-1 and Ki67 expression. Western blot analysis was conducted to assess the expression of TANK-binding kinase 1 (TBK1), macrophage polarization markers (iNOS and arginase-1), and apoptosis-related proteins (MCL-1, Bcl-xL, and Bcl-2). Flow cytometry was employed to quantify macrophage phenotype distributions. TBK1 expression was significantly elevated in LLC tumor tissues. MCP-1 was found to colocalize with the M2 macrophage marker CD206. The combination therapy resulted in a significant reduction in Ki67 expression. arginase-1 expression decreased significantly, while iNOS expression indicated an upward trend, though the change was not statistically significant. Levels of the antiapoptotic proteins MCL-1 and Bcl-xL were significantly downregulated ( P < 0.05), whereas Bcl-2 levels did not differ significantly from those in the control group ( P > 0.05). Flow cytometric analysis indicated a significant decrease in M2 macrophages (F4/80+CD206+) in the intervention group, with no substantial change observed in the proportion of M1 macrophages (F4/80+CD86+). Combined administration of amlexanox and anti-MCP-1 mAb inhibited tumor cell proliferation, promoted apoptosis, and reduced infiltration of tumor-associated M2 macrophages, thereby contributing to suppression of tumor progression in the LLC murine model.
First-line lorlatinib treatment in a 19-year-old patient with ALK-rearranged pulmonary large-cell neuroendocrine carcinoma: a case report and literature review.
Kemik F, Bulutay P, Kıkılı Cİ … +7 more , Köylü B, Demir N, Değirmenci E, Özer KB, Aydin Meriçöz Ç, Tanju S, Selçukbiricik F
Anticancer Drugs · 2026 Jan · PMID 40626442 · Publisher ↗
Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subtype of nonsmall cell lung cancer, typically occurring in elderly male smokers. Its occurrence in the adolescent population is exceptional...
Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subtype of nonsmall cell lung cancer, typically occurring in elderly male smokers. Its occurrence in the adolescent population is exceptionally uncommon, with only a handful of cases reported in the literature. Even more rarely, LCNEC harbors ALK fusions, an unusual molecular alteration with important therapeutic relevance. We report a 19-year-old female patient who presented with bone pain and was found to have widespread skeletal and mediastinal lymph node involvement. Initial workup revealed elevated serum calcitonin and carcinoembryonic antigen (CEA) levels, and histopathology showed high-grade neuroendocrine carcinoma with immunoreactivity for chromogranin, synaptophysin, CD56, as well as calcitonin and CEA. Due to the neuroendocrine phenotype and calcitonin positivity, metastatic medullary thyroid carcinoma was initially suspected. However, thyroid fine needle aspiration from the suspicious thyroid nodule did not provide any evidence in this direction, and the RET mutation testing was also negative. Further molecular analysis revealed an EML4-ALK fusion and a TP53 mutation in tumor tissue. The patient was diagnosed with ALK-positive LCNEC and treated with lorlatinib and denosumab combination. A marked clinical and metabolic response was achieved within 3 months of treatment initiation. To our knowledge, this is the first reported case of ALK-rearranged pulmonary LCNEC in an adolescent patient treated with a tyrosine kinase inhibitor. This case underscores the extreme rarity of LCNEC in adolescents, highlighting that ALK rearrangements, although exceptionally rare in this histological subtype, can have significant therapeutic implications. It further emphasizes the importance of routine molecular profiling in atypical clinical scenarios and supports the utility of targeted therapies in rare tumor subsets.
The mTOR pathway inhibition with everolimus in pseudomyogenic hemangioendothelioma harboring SERPINE1-FOSB gene fusion: a case report and review of the literature.
Kikili Cİ, Köylü B, Kemik F … +3 more , Demir N, Deveci MA, Selçukbiricik F
Anticancer Drugs · 2025 Oct · PMID 40601409 · Publisher ↗
Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare tumor that is frequently misdiagnosed as other vascular or soft tissue neoplasms and typically follows an indolent course. Due to its locally aggressive and...
Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare tumor that is frequently misdiagnosed as other vascular or soft tissue neoplasms and typically follows an indolent course. Due to its locally aggressive and multifocal nature, surgical intervention is often not feasible. Moreover, conventional chemotherapy has shown limited efficacy according to existing literature. Recent advances in genetic profiling have identified a SERPINE1/FOSB gene fusion in PHE, leading to the activation of the mechanistic target of rapamycin (mTOR) pathway. This discovery has highlighted mTOR inhibitors and multityrosine kinase inhibitors as promising therapeutic options. In this report, we present a PHE case with confirmed SERPINE1/FOSB fusion who was initiated on everolimus therapy, along with a review of the current literature.
FH-2001 is a novel FGFR/VEGFR dual inhibitor with immune-modulating activity.
Liu A, Huang L, Gao X … +4 more , Liu L, Li X, Yu X, Zhao C
Anticancer Drugs · 2025 Oct · PMID 40552364 · Publisher ↗
Multiple cancers are driven by aberrant fibroblast growth factor receptor (FGFR) signaling and vascular endothelial growth factor receptor (VEGFR)-linked angiogenesis. Several therapeutic agents targeting FGFR and VEGFR...
Multiple cancers are driven by aberrant fibroblast growth factor receptor (FGFR) signaling and vascular endothelial growth factor receptor (VEGFR)-linked angiogenesis. Several therapeutic agents targeting FGFR and VEGFR have been developed and approved for use in solid cancers; however, there is still a high unmet medical need for new agents that have a more powerful antitumor activity and a broader antitumor spectrum. Here, we report the discovery of FH-2001, a novel and potent FGFR/VEGFR dual inhibitor, with additional activity of modulating programmed cell death ligand 1 (PD-L1) gene expression. In biochemical assays, FH-2001 showed potent inhibition of FGFR1, 2, 3, and 4, with half-maximal inhibitory concentration (IC 50 ) of 0.2, 0.2, 0.4, and 2.0 nM, respectively, and VEGFR1, 2, and 3, with IC 50 values of 2.0, 0.3, and 0.5 nM, respectively. FH-2001 significantly suppressed the cell growth of FGFR- or VEGFR-driven cancer cell lines. In representative cell line- and patient-derived tumor xenografts with aberrant FGFR or VEGFR signaling, FH-2001 substantially inhibited tumor growth. Furthermore, FH-2001 demonstrated marked antitumor activities when treated alone or combined with PD-L1 or PD-1 antibody in syngeneic mouse models. Flow cytometric analysis revealed that FH-2001 alone or in combination with anti-PD-L1 increased T and natural killer cells and decreased myeloid cells in the tumor microenvironment. Mechanistically, FH-2001 treatment dramatically reduced c-Myc and PD-L1 mRNA and protein levels in a dose-dependent manner in vitro . Taken together, FH-2001 is a promising dual-target inhibitor of FGFR and VEGFR and also modulates cancer immunity, while its robust antitumor activity positions it as a potentially class-leading anticancer agent.
Exploring natural products for allosteric inhibition of glutathione peroxidase 4 in drug-resistant cancers via molecular docking and dynamics.
Yasir M, Patra J, Maurya RK … +2 more , Tripathi AS, Pathan HK
Anticancer Drugs · 2025 Oct · PMID 40549449 · Publisher ↗
Glutathione peroxidase 4 (GPX4) plays a pivotal role in regulating ferroptosis and maintaining redox homeostasis, making it a critical target in drug-resistant cancers. Recent studies suggest that allosteric inhibition o...
Glutathione peroxidase 4 (GPX4) plays a pivotal role in regulating ferroptosis and maintaining redox homeostasis, making it a critical target in drug-resistant cancers. Recent studies suggest that allosteric inhibition of GPX4 could overcome resistance mechanisms. This study aimed to identify natural products with potential allosteric inhibition of GPX4 using computational approaches. A comprehensive virtual screening was conducted on a curated library of 125 415 natural compounds derived from the COlleCtion of Open Natural ProdUcTs (COCONUT) database. Structure-based virtual screening and molecular docking were performed against the allosteric site of GPX4 (PDB ID: 7U4N) using UCSF DOCK6. The top candidates were evaluated through binding free energy calculations [molecular mechanics Poisson-Boltzmann surface area (MM-PBSA)] and 100 ns molecular dynamics simulations using the AMBER20 package. Pharmacokinetic and toxicity profiles were assessed through absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. Five natural compounds - quercetin, zeatinriboside, ribofuranosylmakaluvic acid C, tecleanatalensine B, and scopolamine - exhibited superior binding affinities (docking scores ranging from -4.01 to -4.95 kcal/mol) compared with the cocrystallized ligand (-3.15 kcal/mol), with significant interactions at the key Cys66 residue of GPX4. MM-PBSA analysis revealed highly favorable binding free energies (up to -37.94 kcal/mol), indicating stable ligand-protein complexes. Molecular dynamic simulations confirmed structural stability, with minimal root mean square deviation and root mean square fluctuations. ADMET profiling suggested favorable solubility, absorption, low toxicity, and good drug-likeness. This study highlights the potential of natural products as allosteric inhibitors of GPX4. The identified compounds demonstrated strong and stable interactions with the GPX4 allosteric site and possessed desirable pharmacokinetic properties, warranting further in-vitro and in-vivo investigations for potential development as anticancer agents targeting drug-resistant cancers.
Discovery and optimization of oxidative phosphorylation inhibitors from a phenotypic screen.
El Shemerly M, Richalet F, Robay D … +10 more , Nuoffer C, Kunz A, Bury L, Hisler C, Hermann N, Spickermann J, Weiler S, McSheehy PMJ, Kellenberger L, Lane HA
Anticancer Drugs · 2025 Oct · PMID 40536826 · Publisher ↗
Tumor metabolism and metabolic reprogramming in cancer cells represent a promising area in oncology research, offering new avenues for therapeutic intervention. While the 'Warburg effect' highlights the reliance of many...
Tumor metabolism and metabolic reprogramming in cancer cells represent a promising area in oncology research, offering new avenues for therapeutic intervention. While the 'Warburg effect' highlights the reliance of many tumors on aerobic glycolysis, emerging evidence indicates that some cancers also depend on mitochondrial oxidative phosphorylation (OXPHOS) for energy production, cancer cell survival, tumor progression, metastasis, and drug resistance. We conducted a high-throughput, differential, phenotypic screening followed by a focused medicinal chemistry campaign, leading to the identification of novel, potent OXPHOS inhibitors. These lead compounds selectively target complex I of the mitochondrial electron transport chain, thereby disrupting ATP production and oxygen consumption in cancer cells. In-vitro studies in breast cancer cell lines, along with published data, suggest that MCT4 expression may serve as a biomarker for drug sensitivity. Notably, low MCT4 expression correlated with higher potency in cell growth assays. The identified compounds exhibited favorable drug-like properties, including good pharmacokinetics and oral bioavailability in mice. Daily oral dosing significantly inhibited tumor growth in two in-vivo breast cancer models with low MCT4 expression levels. This efficacy, however, was accompanied by body weight loss, indicating the need to enhance the therapeutic index through optimization or rational combination therapy strategies. These findings highlight the therapeutic potential of targeting mitochondrial OXPHOS in cancers with defined metabolic dependencies, offering a novel approach for exploiting tumor-specific metabolic vulnerabilities for improved cancer treatment.
Dysfunction of core clock genes regulates malignant phenotype and gemcitabine sensitivity of cholangiocarcinoma cells.
Li Y, Zheng A, Cui Y … +1 more , Liu T
Anticancer Drugs · 2025 Oct · PMID 40526442 · Full text
The circadian clock governs daily rhythms in numerous physiological processes through precise regulation of gene expression and biochemical functions. Dysregulation of the circadian rhythm has been implicated in carcinog...
The circadian clock governs daily rhythms in numerous physiological processes through precise regulation of gene expression and biochemical functions. Dysregulation of the circadian rhythm has been implicated in carcinogenesis and cancer progression. However, the mechanisms by which the circadian clock influences cancer phenotype and chemotherapy resistance, particularly in cholangiocarcinoma (CCA), remain poorly understood. Using cell lines established from primary CCA and metastatic ascites of two male patients, we manipulated core clock genes ( BMAL1 , PER2 , and NR1D1 ) to evaluate their effects on circadian rhythms. We analyzed alterations in circadian phenotypes at dynamic and single time points and assessed their impact on cancer-related phenotypic changes, including proliferation, apoptosis, cell cycle regulation, migration, invasion, and the expression of epithelial-to-mesenchymal transition (EMT) and cancer stem cell markers. Additionally, we examined the impact of circadian disruption on gemcitabine sensitivity. Genetic deletion of BMAL1 , PER2 , and NR1D1 disrupted circadian rhythm and significantly altered cancer phenotypes. Notably, BMAL1 and NR1D1 impairment exacerbated cell migration, invasion, and EMT activation in CCA cells. BMAL1 loss also induced gemcitabine resistance. In contrast, PER2 repression enhanced chemosensitivity and inhibited metastasis. The modulation of the circadian gene triggered phenotypic changes in CCA cells, indicating a crucial involvement of core-clock components in the pathological mechanisms hastening bile duct cancer malignancy. Our findings advance the understanding of regulating CCA malignancy and may offer a novel target for its treatment.
Novel dibenzoylmethane derivative 2-allyl-1,3-diphenyl-1, 3-propanedione: a safe and effective topical treatment for melanoma.
Baeta JVPB, Rocha E Oliveira MAB, Nascimento FR … +6 more , de Oliveira MR, Pizziolo VR, de Oliveira Mendes TA, Diaz-Muñoz G, Dos Santos AA, Diaz MAN
Anticancer Drugs · 2025 Sep · PMID 40526432 · Publisher ↗
This study investigated 2-allyl-1,3-diphenyl-1,3-propanedione (DPAP), a dibenzoylmethane derivative, as a potentially more effective and safer alternative to dacarbazine for melanoma treatment. The antitumor activity of...
This study investigated 2-allyl-1,3-diphenyl-1,3-propanedione (DPAP), a dibenzoylmethane derivative, as a potentially more effective and safer alternative to dacarbazine for melanoma treatment. The antitumor activity of DPAP was assessed through comprehensive in-vitro, in-silico, and in-vivo experiments. In-vitro assays evaluated DPAP's IC 50 values against melanoma cells, benchmarking its efficacy against dacarbazine. Molecular analyses explored apoptosis mechanisms, emphasizing the roles of FAS receptors and caspase pathways. In-silico absorption, distribution, metabolism, excretion, and toxicity analysis provided insights into DPAP's pharmacokinetic profile, including absorption, distribution, metabolism, and toxicity. In-vivo studies examined its effects on tumor volume, vascular endothelial growth factor (VEGF) levels, and the histopathology of the liver, kidney, and lymph nodes. DPAP demonstrated significantly enhanced antitumor activity, reflected by markedly lower IC 50 values compared with dacarbazine, underscoring its superior efficacy and specificity toward tumor cells. Molecular assays confirmed that DPAP induces apoptosis through modulation of FAS receptors and activation of caspase pathways. In-silico results revealed favorable pharmacokinetic properties, including high intestinal absorption and good tissue distribution, with no evidence of carcinogenic potential. Notably, in-vivo experiments showed that DPAP effectively reduced tumor volume and VEGF levels, while also preventing hepatotoxicity and nephrotoxicity. In addition, it inhibited the migration of tumor cells to lymph nodes. These findings position DPAP as a promising candidate for melanoma treatment, particularly as a topical therapeutic, offering enhanced efficacy and safety compared with existing treatments. DPAP is a promising candidate for melanoma treatment, particularly through topical application, offering a safer and more effective alternative to current treatments.
Progression of drug resistance or multiple primary lung cancer: a case report and literature review of a patient with mesenchymal-epithelial transition factor exon 14 skipping alterations lung adenocarcinoma.
Gong L, Zhou L, Yang P … +3 more , Xiong F, Li X, Tang C
Anticancer Drugs · 2025 Oct · PMID 40512522 · Full text
Mesenchymal-epithelial transition factor (MET) exon 14 skipping alterations are rare mutations in non-small-cell lung cancer, associated with high malignancy and poor prognosis. This article presents a case of a patient...
Mesenchymal-epithelial transition factor (MET) exon 14 skipping alterations are rare mutations in non-small-cell lung cancer, associated with high malignancy and poor prognosis. This article presents a case of a patient diagnosed with advanced left upper lung adenocarcinoma characterized by a MET14 skipping mutation. Following first-line treatment with crizotinib, there was a significant reduction in the size of the primary lesion; however, during the course of treatment, an increase in size and prominence of solid components were observed in the right upper lung lesion. A biopsy and subsequent genetic testing revealed an epidermal growth factor receptor L858R mutation in the right upper lung adenocarcinoma, indicating the presence of multiple primary lung cancers. The patient opted against surgical intervention and local treatments, choosing instead a combination therapy regimen that included almonertinib and crizotinib. This treatment approach led to a significant reduction in the size of the right upper lung lesion. The patient's condition has remained stable without any signs of progression, resulting in an overall survival duration exceeding 53 months.
α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis.
Yu J, Xue Y, Gao Z … +4 more , Hu L, Liu X, He X, Wang X
Anticancer Drugs · 2025 Sep · PMID 40511788 · Full text
Pancreatic cancer is characterized by aggressiveness and poor prognosis. The development of gemcitabine resistance, especially tumor-associated macrophage (TAM) -induced resistance in the tumor microenvironment, has grea...
Pancreatic cancer is characterized by aggressiveness and poor prognosis. The development of gemcitabine resistance, especially tumor-associated macrophage (TAM) -induced resistance in the tumor microenvironment, has greatly limited its therapeutic effectiveness. This study investigates the effects and underlying mechanisms of the plant-derived bioactive compound α-asarone in reversing gemcitabine resistance induced by TAMs in pancreatic cancer, offering potential therapeutic alternatives. Flow cytometry was used to assess the cell cycle and apoptosis in pancreatic cancer cells. Transforming growth factor-beta 1 (TGF-β1) secretion was measured by ELISA, and Cell Counting Kit-8 assays to evaluate the survival of PANC-1 cells treated with gemcitabine. Western blotting and quantitative real-time PCR were used to analyze growth factor independent 1 (Gfi-1) expression and its association with gemcitabine resistance. α-Asarone effectively reversed gemcitabine resistance in pancreatic cancer cells. Treatment with α-asarone reduced TGF-β1 levels in TAM condition medium, which in turn led to the upregulation of Gfi-1 expression. Gfi-1 was found to negatively regulate the expression of drug resistance factors, including connective tissue growth factor (CTGF) and high mobility group box 1 (HMGB1), thereby reversing gemcitabine resistance in pancreatic cancer cells. Those results indicate that α-asarone enhances Gfi-1 expression, downregulates CTGF and HMGB1, and restores gemcitabine sensitivity by reducing TGF-β1 secretion from TAMs. α-Asarone can effectively reverse gemcitabine resistance in pancreatic cancer by reducing TGF-β1 secretion from TAMs, upregulating Gfi-1, and downregulating resistance factors such as CTGF and HMGB1. This restoration of gemcitabine sensitivity may improve the therapeutic efficacy of gemcitabine in pancreatic cancer treatment.
First-line treatment with a combination of immunotherapy, anti-EGFR monoclonal antibodies, and chemotherapeutics for unresectable left KRAS/BRAF wild-type microsatellite-stable colorectal cancer: a case report.
Zhang Y, Wang D, Zhang K … +2 more , Li S, Yu C
Anticancer Drugs · 2025 Sep · PMID 40460045 · Publisher ↗
Immunotherapy shows limited efficacy in microsatellite-stable (MSS) colorectal cancer. This case report describes a 40-year-old male with left-sided kirsten rat sarcoma viral oncogene homolog (KRAS)/v-raf murine sarcoma...
Immunotherapy shows limited efficacy in microsatellite-stable (MSS) colorectal cancer. This case report describes a 40-year-old male with left-sided kirsten rat sarcoma viral oncogene homolog (KRAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type, MSS colorectal cancer and liver metastases who achieved complete regression of metastases following first-line treatment with toripalimab, cetuximab, and FOLFIRI (irinotecan + fluorouracil + leucovorin), enabling curative-intent surgical resection. The patient achieved a progression-free survival of 16 months and an overall survival exceeding 20 months. The regimen demonstrated excellent tolerability without severe adverse events, suggesting that this triple combination represents a promising strategy for conversion therapy in advanced MSS colorectal cancer.
Benefit of switching to firmonertinib following almonertinib-induced interstitial pneumonitis in a patient with advanced non-small-cell lung cancer: a case report.
Wang L, Yang P, Luo H
Anticancer Drugs · 2025 Sep · PMID 40460030 · Full text
Almonertinib, a representative epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the first-line standard treatment for EGFR-mutant advanced non-small-cell lung cancer; however, it may induce drug-...
Almonertinib, a representative epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the first-line standard treatment for EGFR-mutant advanced non-small-cell lung cancer; however, it may induce drug-related interstitial lung disease (ILD). This case report presents a 67-year-old female with advanced lung adenocarcinoma, who was diagnosed with an EGFR exon 19 deletion mutation. After 2 months of first-line almonertinib treatment (110 mg/day), a PR was achieved; however, progressive respiratory distress emerged. Chest computed tomography revealed ground-glass opacities accompanied by grid-like changes in both lungs, leading to a diagnosis of EGFR-TKI-related ILD (grade 2). Following glucocorticoid treatment and medication discontinuation, the lung lesions improved. Given the persistent tumor activity, the patient was switched to firmonertinib (80 mg/day) for targeted therapy. This switch did not lead to a recurrence of ILD symptoms, with a progression-free survival exceeding 5 months and good tolerability. This suggests that for patients with ILD associated with almonertinib and firmonertinib may serve as an effective and safe alternative. Closely monitoring ILD in clinical practice and promptly switching to similar drugs may avoid chemotherapy intervention and optimize treatment strategies. This case marks the first report of clinical experience achieving sustained remission by switching to a similar drug, firmonertinib, in patients with ILD related to almonertinib.
Denticleless homolog-mediated ubiquitin-proteasome degradation of forkhead box O1 contributes to development of carboplatin resistance in retinoblastoma.
Liu X, Jiao SF, Liu CY … +3 more , Luo R, Liu H, Chai Y
Anticancer Drugs · 2025 Sep · PMID 40455648 · Publisher ↗
This study aimed to investigate the role of forkhead box O1 (FOXO1) in carboplatin-resistant retinoblastoma (RB) cells, focusing on its subcellular distribution and regulation through ubiquitin-dependent degradation medi...
This study aimed to investigate the role of forkhead box O1 (FOXO1) in carboplatin-resistant retinoblastoma (RB) cells, focusing on its subcellular distribution and regulation through ubiquitin-dependent degradation mediated by denticleless homolog (DTL). The study sought to elucidate the molecular mechanisms underlying carboplatin resistance in RB and explore potential therapeutic strategies to overcome chemoresistance. Carboplatin-resistant RB cell lines (Y79/CBP and WERI-Rb-1/CBP) were established by incremental drug exposure. Bioinformatics analysis of the GSE111168 dataset identified differentially expressed genes associated with ubiquitination pathways. DTL expression was modulated using adeno-associated virus-mediated knockdown and overexpression. FOXO1 protein levels, subcellular localization, and ubiquitination were assessed via western blotting, immunofluorescence, and coimmunoprecipitation (Co-IP). The effects of DTL knockdown and LOM612 treatment on cell proliferation, apoptosis, and tumor growth were evaluated in vitro and in vivo using xenograft models. FOXO1 expression and nuclear localization were significantly reduced in carboplatin-resistant RB cells, with elevated levels of FOXO1 ubiquitination. Proteasome inhibitors preserved FOXO1 protein levels, implicating the ubiquitin-proteasome system in its degradation. DTL was identified as a significantly overexpressed gene in both resistant cells and patient-derived samples. Silencing DTL increased FOXO1 protein expression and nuclear accumulation, while Co-IP confirmed the interaction between DTL and FOXO1, mediated by the WD40 domain of DTL. Combined DTL knockdown and LOM612 treatment synergistically inhibited cell proliferation and invasion, promoted apoptosis in vitro, and significantly reduced tumor growth and induced apoptosis in vivo. DTL-mediated ubiquitination and degradation of FOXO1 play a critical role in carboplatin resistance in RB. Dual targeting of DTL and FOXO1 nuclear translocation may represent a promising therapeutic strategy to overcome chemoresistance and improve clinical outcomes in RB.
APG-115 synergizes with bortezomib to induce apoptosis in cervical cancer cells.
Sun C, Meng X, Cui X … +8 more , Liang S, Sun J, Zhang B, Cui Y, Zhao Y, Chen N, Tian K, Chen Y
Anticancer Drugs · 2025 Sep · PMID 40455647 · Full text
Despite significant advancements in vaccination, screening, and therapeutic strategies have substantially reduced cervical cancer incidence, effective treatment for this disease remains a major clinical challenge. This s...
Despite significant advancements in vaccination, screening, and therapeutic strategies have substantially reduced cervical cancer incidence, effective treatment for this disease remains a major clinical challenge. This study reveals that APG-115, a murine double minute 2 (MDM2) inhibitor, upregulates the transcription and expression of MDM2, p53, and p21, effectively inhibiting cell proliferation and inducing apoptosis in cervical cancer cells. Mechanistically, APG-115 suppresses the activation of the AKT and ERK signaling pathways and reduces the expression of antiapoptotic proteins BCL-2, BCL-xL, and MCL-1, while promoting the expression of pro-apoptotic proteins BAK, BAX, and BIM. Notably, the combination of APG-115 with bortezomib enhances p53 and p21 expression, synergistically induces cell apoptosis. In the cervical cancer xenograft models, APG-115 and bortezomib significantly downregulated the expression of Ki67 and BCL-2 while markedly increasing p21 protein levels, effectively suppressing tumor growth and inducing apoptosis. The combination further amplified the effects on Ki67, BCL-2, and p21 expression, leading to enhanced tumor growth inhibition. In summary, this study demonstrates that APG-115 exerts antitumor effects in cervical cancer, and its combination with bortezomib further enhances this inhibitory effect, probably through maximal activation of p53 and inhibition of BCL-2, suggesting a potential application of APG-115 in the treatment of cervical cancer.
Early sensitivity and rapid resistance to drug therapy in primary pulmonary nuclear protein in testis carcinoma.
Ma J, Tian Y, Zhang Y … +5 more , Song L, Zhen X, Sang J, Meng D, Ye X
Anticancer Drugs · 2025 Sep · PMID 40439574 · Publisher ↗
Nuclear protein in testis (NUT) carcinoma is a rare disease characterized by aggressive and rapid progression. There is no standard management of primary pulmonary NUT carcinoma until now, and the median overall survival...
Nuclear protein in testis (NUT) carcinoma is a rare disease characterized by aggressive and rapid progression. There is no standard management of primary pulmonary NUT carcinoma until now, and the median overall survival is only 4.4 months. Here, we describe a case where a 48-year-old woman presented with a dry, lasting half a month, and she was diagnosed with primary pulmonary NUT carcinoma and was given chemotherapy, immunotherapy, antiangiogenesis therapy, and palliative radiotherapy. When secondary tumor progression, she was conducted an organoid drug sensitivity test for better guide therapy. The initial two cycles of first-line and second-line treatments in our patient proved effective and improved the overall survival to more than 8 months. This is the first report of the use of an organoid drug sensitivity test for primary pulmonary NUT carcinoma. It provides a new approach for selecting drugs, particularly when multiple lines of treatment have proven ineffective and the next steps are unclear.
A case of diabetic ketoacidosis triggered by immune checkpoint inhibitors in the treatment of recurrent nasopharyngeal carcinoma.
Xian S, Yang L, Wang C … +3 more , Cao J, Jiang D, Huang J
Anticancer Drugs · 2025 Sep · PMID 40439560 · Publisher ↗
Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) have been widely documented. Diabetic ketoacidosis (DKA), a severe irAEs, has not been previously reported in patients with nasopharynge...
Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) have been widely documented. Diabetic ketoacidosis (DKA), a severe irAEs, has not been previously reported in patients with nasopharyngeal carcinoma (NPC). This case report describes the development of DKA during maintenance immunotherapy with tislelizumab in a patient with recurrent NPC. A 41-year-old female patient with recurrent NPC (rT3N0M0, 8 th edition of AJCC staging) experienced DKA during her 13 th session of maintenance treatment with the ICI tislelizumab. After urgent consultation with an endocrinologist, immune-related DKA was diagnosed, and immune checkpoint inhibitor-related diabetes was confirmed. Prompt treatment with hypoglycemic agents, fluid infusion, and correction of water-electrolyte and acid-base balance was administered. The patient's blood glucose was stabilized within 6 days, and she was discharged without complications. This is the first reported case of DKA in a patient with NPC receiving tislelizumab maintenance immunotherapy. Clinicians should enhance their understanding and monitoring of adverse events in patients treated with ICIs, focusing on early diagnosis and appropriate intervention.
Rapid radiological response of leptomeningeal carcinosis and prolonged survival to encorafenib and binimetinib in BRAF-mutated melanoma.
Corradi G, De Martino S, Rinaldi A … +4 more , Siepe G, Marchese PV, Melotti B, Comito F
Anticancer Drugs · 2025 Sep · PMID 40439484 · Publisher ↗
Among solid tumors, malignant melanoma (MM) has the highest risk of metastasis to the leptomeninges, for which a specific therapeutic regimen has not been established yet. This case report describes a rapid partial respo...
Among solid tumors, malignant melanoma (MM) has the highest risk of metastasis to the leptomeninges, for which a specific therapeutic regimen has not been established yet. This case report describes a rapid partial response to leptomeningeal disease (LMD) in a patient with a BRAF V600K-mutated MM. A 69-year-old man affected by metastatic melanoma was initially treated with benefit with targeted therapy with encorafenib and binimetinib, which was discontinued several times because of toxicity or intolerance, and then with dabrafenib and trametinib, which were also poorly tolerated. During the treatment pause, the patient, who had refused to receive immunotherapy developed LMD and was started again on targeted therapy with reduced dosage of encorafenib and binimetinib. A few days after starting this treatment, MRI showed an important reduction of the perilesional edema and then, after a few months, a disease response. The patient had a long survival of approximately 14 months from this diagnosis. To the best of our knowledge, this is the first report describing rapid radiological response, clinical benefit, and prolonged survival with encorafenib and binimetinib in patients affected by LMD from melanoma.
Synthesis, characterization and evaluation of linoleic acid-loaded nano-carriers: a novel drug delivery system for efficient treatment of hepatocellular carcinoma.
Ghasemzad M, Bakhshandeh H, Naserkhaki R … +8 more , Ghoytasi I, Shokoohian B, Fotouhi A, Miri-Lavasani Z, Rismani E, Hossein-Khannazer N, Piryaei A, Vosough M
Anticancer Drugs · 2025 Sep · PMID 40439273 · Publisher ↗
Hepatocellular carcinoma is the main primary liver cancer. Due to the high recurrence rate and potential resistance to treatments, there is an urgent need to find more effective and targeted therapies. Combinational ther...
Hepatocellular carcinoma is the main primary liver cancer. Due to the high recurrence rate and potential resistance to treatments, there is an urgent need to find more effective and targeted therapies. Combinational therapies and using advanced drug delivery methods are promising approaches. Niosomes are one of the popular types of nanoparticles in modern drug delivery systems and have recently attracted more attention. They are biodegradable, nonimmunogenic, and more stable carriers than liposomes. They can release anticancer drugs in an efficient and controlled manner. The aim of this study was to synthesize and characterize the physicochemical properties of linoleic acid (LA)-loaded niosomes and evaluate their anticancer effects on a hepatoma cell. We synthesized LA-loaded niosomes using a thin-film hydration method and characterized their size, polydispersity index (PDI), and zeta potential. The morphology of niosomes was evaluated by scanning electron microscopy. Finally, the viability, migration capacity, and colonization potential of Hep-3B hepatoma cells treated with 150 μM LA-loaded niosomes were investigated and compared to the control groups. The niosomes had a mean size of 266.9 nm, PDI of 0.271, and zeta potential of -26.1 mV. The LA-loaded niosomes released LA sustainably at 37 °C for 72 h. MTS assay indicated that the LA-loaded niosomes were more toxic than free LA. Hep-3B hepatoma cells treated with LA-loaded niosomes showed a remarkable decline in the migration ability and colony-formation capacity. Therefore, the use of LA-loaded niosomes in combination with conventional protocols may be a promising approach to target cancer cells.
Anlotinib for the treatment of pulmonary epithelioid inflammatory myofibroblastic sarcoma: a case report.
Zeng H, Li X, Chen S … +3 more , Xu J, Xiao Y, Zhao Y
Anticancer Drugs · 2025 Sep · PMID 40353528 · Full text
Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare subtype of inflammatory myofibrosarcoma. Anlotinib has demonstrated efficacy in the treatment of sarcoma. Nevertheless, to our knowledge, its use in EIMS...
Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare subtype of inflammatory myofibrosarcoma. Anlotinib has demonstrated efficacy in the treatment of sarcoma. Nevertheless, to our knowledge, its use in EIMS has not been reported. Herein, we present a case of pulmonary EIMS. The patient underwent two courses of chemotherapy with doxorubicin combined with ifosfamide; however, the treatment was switched to anlotinib due to leukocytopenia. After 11 months of treatment with anlotinib, the tumor was in partial remission. Subsequently, the patient developed an acute myocardial infarction, which resulted in the discontinuation of anlotinib. Four months after discontinuation, the tumor progressed and anlotinib therapy was resumed. Following treatment for 5 months, tumor assessment indicated partial remission until March 2024. During this period, the patient experienced an adverse effect (i.e. ostealgia), which led to two reductions in the dosage of anlotinib. This case report provides a novel strategy for treating EIMS.
Nivolumab- and ipilimumab-induced myositis, myasthenia gravis, and myocarditis in a patient with metastatic melanoma.
Inan B, Duzgun U, Ergul-Ulger Z … +4 more , Bekircan-Kurt CE, Ceylan BN, Karadas O, Odabasi Z
Anticancer Drugs · 2025 Aug · PMID 40343457 · Publisher ↗
Immune checkpoint inhibitors (ICIs) have revolutionized advanced cancer treatment and prolonged survival; however, they are associated with several immune-related adverse events in up to 60% of patients, affecting variou...
Immune checkpoint inhibitors (ICIs) have revolutionized advanced cancer treatment and prolonged survival; however, they are associated with several immune-related adverse events in up to 60% of patients, affecting various organ systems. A 73-year-old male patient with metastatic melanoma was admitted with left-sided ptosis, diplopia, head drop, and proximal muscle weakness. The patient had been undergoing treatment with nivolumab and ipilimumab, and his symptoms emerged 4 days after receiving the second cycle of the immunotherapy regimen. He was diagnosed as having ICI-related myositis, myasthenia gravis (MG), and myocarditis based on electromyography, muscle biopsy, antibody status, troponin level, and cardiac evaluation. ICIs were withdrawn and the patient was treated with intravenous methylprednisolone, intravenous immunoglobulin, and plasma exchange; however, the patient was treatment-refractory, necessitating long-term immunosuppression with rituximab. Subsequently, he responded well, and nivolumab monotherapy was resumed. The patient has been neurologically stable for 4 months without any recurrence of ICI-related adverse effects. ICI-related myositis, MG, and myocarditis are rare but can be severe and potentially life-threatening. Therefore, early recognition and immediate treatment are crucial for improving prognosis. To the best of our knowledge, this is the only case with nivolumab- and ipilimumab-induced triple overlap syndrome successfully treated with rituximab.
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