Anti-cancer Drugs[JOURNAL]
Sun
200 papers
Reply to: Association between nilotinib-induced hyperbilirubinemia and UGT1A1 polymorphisms in a chronic myeloid leukemia patient.
Cattaneo D, Iurlo A
Anticancer Drugs · 2025 Jul · PMID 40341468 · Publisher ↗
Abstract loading — click title to view on PubMed.
Complete response with trastuzumab in heavily pretreated HER2-positive metastatic salivary duct carcinoma.
Çolak R, Kapar C, Yilmaz M
Anticancer Drugs · 2025 Sep · PMID 40327398 · Publisher ↗
Salivary duct carcinoma (SDC), an aggressive and relatively rare tumor, accounts for approximately 10% of all salivary gland malignancies. We report a case of a patient with a metastatic, human epidermal growth factor re...
Salivary duct carcinoma (SDC), an aggressive and relatively rare tumor, accounts for approximately 10% of all salivary gland malignancies. We report a case of a patient with a metastatic, human epidermal growth factor receptor 2 (HER2)-positive parotid SDC efficiently treated with docetaxel and trastuzumab combination after multiple series of chemotherapies. A 61-year-old man presented with SDC. After adjuvant radiotherapy, imaging revealed multiple metastatic lesions in the lungs. Systemic treatment with carboplatin and paclitaxel was initiated. After disease progression, doxorubicin, vinorelbine, and capecitabine were performed. Neurotrophic tropomyosin receptor kinase and AR (androgen receptor) were negative. Immunohistochemistry determined a HER2-positive score of 3. After multiple chemotherapy, the patient was started with combination of docetaxel and trastuzumab. A complete response was obtained after 3 months of treatment in the patient. In conclusion, SDCs are highly aggressive malignant tumors. Targeted therapy with trastuzumab targeting HER2 overexpression is a reasonable option in metastatic settings.
Multimodal treatment with cisplatin for metastatic disease in malignant peripheral nerve sheath tumors: a case report and review.
Hakim R, Salone MC, Bozza G … +2 more , Spinnato P, Longhi A
Anticancer Drugs · 2025 Aug · PMID 40326738 · Publisher ↗
Malignant peripheral nerve sheath tumors (MPNSTs) are rare and have among the worst prognoses among all soft tissue sarcomas, with 5-year overall survival rates ranging from 16 to 52%. We report a case of a 50-year-old m...
Malignant peripheral nerve sheath tumors (MPNSTs) are rare and have among the worst prognoses among all soft tissue sarcomas, with 5-year overall survival rates ranging from 16 to 52%. We report a case of a 50-year-old man with localized dorsal MPNST who developed local recurrence after 1 year and lung metastasis 3 years after diagnosis. He underwent primary tumor resection, two resections for local recurrence, one lung metastasectomy, seven lines of chemotherapy (epirubicin-ifosfamide, cisplatin-etoposide, trabectedin, pazopanib, carboplatin-etoposide, gemcitabine, and ifosfamide), and four courses of stereotactic body radiotherapy for lung metastases. The patient has shown long remission intervals and survival exceeding 7 years, with a good quality of life since the diagnosis of lung metastasis. We conducted a narrative review based on our treatment approach, considering the recent literature and drugs currently available for the treatment of MPNST.
Efficacy of immune checkpoint inhibitors rechallenge and metronomic cyclophosphamide with or without bevacizumab in metastatic nonsmall cell lung cancer.
Musaelyan AA, Odintsova SV, Urtenova MA … +3 more , Solovyova EP, Kindyalova LV, Orlov SV
Anticancer Drugs · 2025 Aug · PMID 40310023 · Publisher ↗
OBJECTIVE: The present study aims to evaluate the efficacy of immune checkpoint inhibitor (ICI) rechallenge in combination with metronomic cyclophosphamide, with or without bevacizumab, in patients with metastatic nonsma...
OBJECTIVE: The present study aims to evaluate the efficacy of immune checkpoint inhibitor (ICI) rechallenge in combination with metronomic cyclophosphamide, with or without bevacizumab, in patients with metastatic nonsmall cell lung cancer (NSCLC) and to investigate the clinical characteristics associated with the response to the therapy. MATERIALS AND METHODS: The study included 43 patients with metastatic NSCLC who responded to ICIs for ≥4 months and subsequently experienced disease progression. The patients then underwent ICI rechallenge along with either oral cyclophosphamide daily alone ( n = 24) or cyclophosphamide and bevacizumab ( n = 19). RESULTS: Combining ICI with cyclophosphamide resulted in an objective response rate (ORR) of 16.7%, disease control rate (DCR) of 75.0%, median progression-free survival (PFS) of 5.8 months, and overall survival (OS) of 15.4 months. Oral cyclophosphamide and bevacizumab cohort achieved an ORR of 26.3%, a DCR of 78.9%, a PFS of 6.8 months, and an OS of 17.6 months. No treatment-related adverse events resulted in the discontinuation of the study therapy in either cohort. Multivariate analysis demonstrated that the absence of an objective response to initial ICIs (OS: P = 0.016), poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) (PFS: P = 0.017, OS: P = 0.032), and a neutrophil-to-lymphocyte ratio (NLR) ≥ 3.8 (PFS: P = 0.004, OS: P = 0.007) were negative predictors of rechallenge therapy. CONCLUSION: The combination showed promising antitumor activity and a well-tolerated safety profile in patients with ICI-pretreated NSCLC. Furthermore, ECOG PS 0-1, objective response, and NLR ≤ 3.8 were predictive of the efficacy of the study therapy.
Palbociclib stimulates CD8 + T cell response in triple-negative breast cancer via regulating phosphoglycerate dehydrogenase.
Sun Y, Li Y, Han Y … +3 more , Liu C, Song Y, Gao G
Anticancer Drugs · 2025 Aug · PMID 40309992 · Publisher ↗
CDK4/6 inhibitors are applied for the treatment of breast cancer. The purpose of this study was to explore the effects of palbociclib (PALB) on triple-negative breast cancer. An in vivo assay was applied to determine the...
CDK4/6 inhibitors are applied for the treatment of breast cancer. The purpose of this study was to explore the effects of palbociclib (PALB) on triple-negative breast cancer. An in vivo assay was applied to determine the effects of PALB on breast cancer. Gene expression was detected using immunohistochemistry. mRNA levels were detected using reverse transcription-quantitative PCR. Protein expression was detected using western blot. The expansion of CD8 + T cell subsets was detected using flow cytometry. We found that PALB treatment promoted the persistence of CD8 + T cells, manifested by the maintenance of stem-like CD8 + T cells and effector T cells. Moreover, PALB downregulated phosphoglycerate dehydrogenase (PHGDH), high levels of which predicted poor prognosis of breast cancer patients. Moreover, overexpression of PHGDH antagonized the effects of PALB and suppressed the persistence of CD8 + T cells. Additionally, PALB enhanced the effects of anti-PD1 immunotherapy and suppressed the tumor growth of breast cancer. In summary, PALB promoted the maintenance of CD8 + memory precursors in breast cancer via downregulating PHGDH.
Deubiquitinating enzyme UCHL1 stabilizes CAV1 to inhibit ferroptosis and enhance docetaxel resistance in nasopharyngeal carcinoma.
Ye Y, Wang P, Wu D … +3 more , Tang F, Shen N, Hou G
Anticancer Drugs · 2025 Aug · PMID 40279201 · Publisher ↗
The overexpression of CAV1 in many cancers is linked to chemotherapy resistance, but the exact mechanisms by which CAV1 contributes to resistance in nasopharyngeal carcinoma (NPC) are not fully known. Our research aims t...
The overexpression of CAV1 in many cancers is linked to chemotherapy resistance, but the exact mechanisms by which CAV1 contributes to resistance in nasopharyngeal carcinoma (NPC) are not fully known. Our research aims to elucidate the potential pathways by which CAV1 contributes to chemotherapy resistance in NPC, providing a basis for developing strategies to overcome resistance. A docetaxel-resistant NPC cell line was established, and CAV1 expression was analyzed in the cell line and the resistant variant using western blot. The sensitivity of the resistant cell line to docetaxel was assessed via cell counting kit-8, colony formation assays, and flow cytometry. Flow cytometry was used to measure lipid reactive oxygen species levels, while kits were employed to determine Fe 2+ and malondialdehyde concentrations. The Ubibrowser database helped identify ubiquitination enzymes that interact with CAV1. The binding relationship between UCHL1 and CAV1 was studied using co-immunoprecipitation and immunofluorescence, which also evaluated the deubiquitination activity of UCHL1 on CAV1. CAV1 is overexpressed in NPC tissues and cells, correlating with adverse patient prognoses. In docetaxel-resistant cells, CAV1 expression is elevated compared to standard NPC cells. Silencing CAV1 increased the sensitivity of these resistant cells to docetaxel. Additionally, treatment with the ferroptosis inducer erastin could counteract the effects of CAV1 overexpression on drug resistance. UCHL1 interacted with CAV1 and inhibited its ubiquitin-mediated degradation pathway. By deubiquitinating CAV1, UCHL1 stabilizes and increases its expression, which inhibits ferroptosis and enhances the resistance of NPC cells to docetaxel.
Enhanced plasma and brain concentrations and medulloblastoma cytotoxicity of asciminib and nilotinib by P-glycoprotein inhibition with tariquidar.
Thompson EM, Cheng L, Spasojevic I
Anticancer Drugs · 2025 Sep · PMID 40279170 · Full text
ABL1 and ABL2 are putative drivers of medulloblastoma leptomeningeal dissemination. ABL1/ABL2 inhibitors, nilotinib and asciminib, are P-glycoprotein substrates. The purpose of this work is to elucidate P-glycoprotein ex...
ABL1 and ABL2 are putative drivers of medulloblastoma leptomeningeal dissemination. ABL1/ABL2 inhibitors, nilotinib and asciminib, are P-glycoprotein substrates. The purpose of this work is to elucidate P-glycoprotein expression in the brain/brain tumors and to determine if P-glycoprotein inhibition increases plasma and brain concentrations and medulloblastoma cytotoxicity of nilotinib and asciminib. ABCB1 (P-glycoprotein) mRNA expression was analyzed from multiple datasets of brain and brain tumor specimens. Cytotoxicity assays of medulloblastoma cells were conducted. In a mouse model, the pharmacokinetics of asciminib and nilotinib, with and without tariquidar, were determined using LC/MS. ABCB1 mRNA expression varied by brain region and was significantly lower in the cerebellum ( P < 0.05). There was a bimodal increase in brain ABCB1 expression at ages 0-3 and 21-23 ( P < 0.05). ABCB1 expression in pediatric brain tumors was similar to normal brain. The addition of tariquidar significantly reduced medulloblastoma cell viability compared to asciminib alone ( P < 0.01). Tariquidar increased asciminib plasma and brain concentrations at 24 h ( P = 0.0005 and P = 0.0002, respectively) and nilotinib brain concentrations at 3 h ( P = 0.0009). Tariquidar increased the area under the curve (AUC) brain : plasma ratio of asciminib from 0.33 to 10.16% and of nilotinib from 1.16 to 9.61%. Tariquidar prolonged the plasma half-life of asciminib from 2.21 to 10.49 h and nilotinib from 7.63 to 14.64 h. P-glycoprotein inhibition increased the brain concentrations, AUC, and half-life of asciminib and nilotinib and increased cytotoxicity in medulloblastoma cells.
9-Hexadecenoic acid inhibits the aggressiveness of gastric cancer via targeting PTPN1/FTH1 signaling.
Wang X, Peng H
Anticancer Drugs · 2025 Aug · PMID 40279138 · Publisher ↗
9-Hexadecenoic acid (9-HA) possesses anti-tumor properties. However, the effects of 9-HA on gastric cancer are scarcely reported. The present study aimed to investigate the effects of 9-HA on gastric cancer. mRNA levels...
9-Hexadecenoic acid (9-HA) possesses anti-tumor properties. However, the effects of 9-HA on gastric cancer are scarcely reported. The present study aimed to investigate the effects of 9-HA on gastric cancer. mRNA levels were detected by reverse transcription quantitative PCR. Protein expression was detected by western blot. Cell behaviors were analyzed using Cell Counting Kit-8, colony formation, transwell, and propidium iodide staining assays. Co-localization of PTPN1 and FTH1 was determined using fluorescence in situ hybridization assay. In vivo assay was conducted to further verify the effects of 9-HA on gastric cancer. 9-HA suppressed the malignant behavior of gastric cancer. Moreover, 9-HA promoted iron-overload-dependent ferroptosis of gastric cancer in vivo and in vitro. Traditional Chinese medicine systems pharmacology predicted that 9-HA could target PTPN1, which was upregulated in gastric cancer cells. PTPN1-mediated phosphorylation of FTH1 contributed to the latter degradation. Overexpressed PTPN1 alleviated the effects of 9-HA, promoting the aggressiveness of gastric cancer and suppressing tumor cell ferroptosis. Interestingly, overexpressed PTPN1 antagonized the effects of 9-HA, promoted tumor growth, and inhibited the ferroptosis of gastric cancer. In summary, 9-HA-mediated downregulation of PTPN1 drives ferroptosis and inhibit the aggressiveness of gastric cancer. Thence, 9-HA may be an alternative strategy for gastric cancer.
Complete regression of choroidal metastases from renal cancer under sunitinib with grade 3 hyperbilirubinemia.
Ben Kridis W, Ben Lassoued R, Trigui A … +1 more , Khanfir A
Anticancer Drugs · 2025 Aug · PMID 40279103 · Publisher ↗
Sunitinib is a small molecule tyrosine kinase inhibitor that is taken by mouth. It works against several kinases, such as vascular endothelial growth factor receptor, c-Kit, and platelet-derived growth factor receptor. W...
Sunitinib is a small molecule tyrosine kinase inhibitor that is taken by mouth. It works against several kinases, such as vascular endothelial growth factor receptor, c-Kit, and platelet-derived growth factor receptor. We report a case of total disappearance of choroid metastases from renal cell carcinoma after 6 months of sunitinib, with grade 3 hyperbilirubinemia.
A fatty acid metabolism-related gene signature can predict poor prognosis in glioma.
Li C, Xue X, Kong J … +1 more , Zhang J
Anticancer Drugs · 2025 Aug · PMID 40278822 · Publisher ↗
Gliomas, arising from supportive glial cells in the central nervous system, present significant challenges in oncology due to their varying aggressiveness and poor prognosis, particularly in high-grade forms. Understandi...
Gliomas, arising from supportive glial cells in the central nervous system, present significant challenges in oncology due to their varying aggressiveness and poor prognosis, particularly in high-grade forms. Understanding the molecular pathways involved in glioma progression is essential for developing effective treatment strategies. This study aimed to develop a fatty acid metabolism (FAM)-related gene signature to better predict poor prognosis in glioma patients, thereby facilitating more targeted therapeutic approaches. We employed the Least Absolute Shrinkage and Selection Operator regression analysis to identify a gene signature associated with FAM from The Cancer Genome Atlas and Chinese Glioma Genome Atlas RNA-seq datasets. Survival analyses, including Kaplan-Meier and Cox regression analyses, were conducted to assess the prognostic value of the identified genes. A total of seven FAM-related genes were associated with survival outcomes in isocitrate dehydrogenase-1 wild-type glioblastoma. The constructed gene signature effectively stratified patients into high-risk and low-risk groups, with high-risk patients demonstrating significantly poorer survival. PTGR1 emerged as the core gene, closely linked to malignant progression and poor prognosis. The FAM-related gene signature developed in this study provides a reliable tool for predicting poor outcomes in glioma patients. PTGR1, identified as a pivotal gene within this signature, may serve as a potential target for future therapeutic interventions, offering promising avenues for enhancing patient survival.
Impact of obesity on cancer therapy outcomes: a multicenter cohort study of 30-day mortality and morbidity.
Tashkandi E
Anticancer Drugs · 2025 Jul · PMID 40237161 · Full text
Obesity is a substantial concern in oncology, influencing cancer characteristics and treatment outcomes. This study investigated whether obesity contributes to increased 30-day mortality and morbidity in patients receivi...
Obesity is a substantial concern in oncology, influencing cancer characteristics and treatment outcomes. This study investigated whether obesity contributes to increased 30-day mortality and morbidity in patients receiving anticancer therapy. In this multicenter retrospective cohort study, patients with cancer were categorized as either normal weight or obese and analyzed based on demographics, cancer types, treatment modalities, and 30-day posttreatment mortality and morbidity rates. Statistical comparisons were performed to determine associations between obesity, treatment type, and clinical outcomes. Among 1635 patients, 46.6% ( n = 760) were of normal weight and 53.4% ( n = 875) were obese. Obesity was more prevalent among female patients, while 60.4% of male patients were of normal weight ( P = 0.001). Substantial associations have been found between obesity and specific cancers, including colorectal cancer, lymphoma, head and neck cancer, and sarcoma. Chemotherapy was more frequently administered to patients with obesity (62.5%, P = 0.001), while hormonal therapy was predominantly administered to patients with normal weight (81.8%). Patients with normal weight exhibited a higher 30-day mortality rate (74.5%, P = 0.05), although morbidity rates did not differ substantially between the weight groups. Obesity is associated with specific cancer types and influences treatment selection, but it does not independently increase the incidence of short-term treatment complications. These findings suggest that the effect of obesity is more prominent in terms of cancer type and treatment choice than in predicting short-term morbidity. Further studies are warranted to elucidate the long-term effects of obesity on cancer outcomes.
Real-life data on adjuvant trastuzumab emtansine treatment in early-stage HER2-positive breast cancer: a Turkish Oncology Group study.
Akturk Esen S, Seven I, Akdere Ates G … +19 more , Colak R, Kinikoglu O, Akay Hacan B, Bakkal Temi Y, Sever N, Kahraman S, Arak H, Topcu A, Saray S, Akbas S, Beypinar İ, Acar O, Erdoğan AP, Yilmaz M, Isik D, Ates O, Cabuk D, Sendur MAN, Uncu D
Anticancer Drugs · 2025 Aug · PMID 40162996 · Publisher ↗
In this Turkish Oncology Group study, we aimed to evaluate the effectiveness of trastuzumab emtansine (TDM1) in the adjuvant treatment of early-stage human epidermal growth factor receptor-2 (HER2)-positive breast cancer...
In this Turkish Oncology Group study, we aimed to evaluate the effectiveness of trastuzumab emtansine (TDM1) in the adjuvant treatment of early-stage human epidermal growth factor receptor-2 (HER2)-positive breast cancer with residual disease using real-life data. A total of 13 Turkish centers participated in the study between September 2019 and October 2024. Patients with early-stage HER2-positive breast cancer who underwent surgery after completing neoadjuvant chemotherapy with HER2-targeted therapies had residual invasive disease in the breast or axillary lymph nodes and received adjuvant TDM1 therapy. The patients' files were retrospectively scanned from the hospitals' archives. The study included 79 female patients. The 36-month median disease-free survival rate was 92%, and the 36-month median overall survival rate was 85%. Neoadjuvant anthracyclines were administered to 93.6% of the patients. All patients received neoadjuvant trastuzumab and 86.1% of patients received neoadjuvant pertuzumab in addition to trastuzumab. Twelve (15.2%) patients developed progression during or after adjuvant TDM1 therapy. The most common adverse events were grade 1 fatigue (34.2%), grade 1 anemia (27.8%), and grade 1 AST increase (25.3%). Toxicity of grade 3 or above developed in five (5%) patients. TDM1 was stopped for one patient due to thrombocytopenia and for two patients due to cardiotoxicity. This study describes the sociodemographic and clinicopathological characteristics of patients with early-stage HER2-positive breast cancer with residual disease after neoadjuvant therapy and provides real-life data on treatment with adjuvant TDM1. The findings support the manageable safety profile of the adjuvant TDM1 regimen with a low discontinuation rate.
Correlative analysis of immune-related thyroid dysfunction and prognosis in patients with advanced esophageal squamous cell carcinoma.
Da L, Qu Z, Zhang Y … +2 more , Da J, Gu K
Anticancer Drugs · 2025 Jul · PMID 40112209 · Publisher ↗
To explore the clinical characteristics of immune-related thyroid dysfunction (TD) and its correlation with prognosis. By collecting the clinical data of 116 patients with advanced esophageal squamous cell carcinoma (ESC...
To explore the clinical characteristics of immune-related thyroid dysfunction (TD) and its correlation with prognosis. By collecting the clinical data of 116 patients with advanced esophageal squamous cell carcinoma (ESCC) who received programmed death receptor-1 (PD-1) inhibitor treatment, we analyzed the clinical characteristics of immune-related TD and its influencing factors and compared the prognostic differences among patients in different groups. Immune-related TD occurred in 45 (38.8%) patients after PD-1 inhibitor treatment, and the median time to its occurrence was 11.3 weeks. The toxicity of immune-related TD was grade 1 or grade 2 and only required symptomatic treatment. Female patients, as well as those with an Eastern Cooperative Oncology Group Performance Status less than equal to 1, no lymph node metastasis, no history of drinking, and high baseline thyroid-stimulating hormone levels, were likely to develop immune-related TD. Compared with the patients in the group without immune-related TD [TD(-)], the median progression-free survival (mPFS) and median overall survival (mOS) of the patients in the immune-related TD [TD(+)] group were significantly prolonged (mPFS: 12.6 vs. 6.5 months, P = 0.001; mOS: 20.2 vs. 11.2 months, P < 0.001). Further subgroup analysis showed that compared with the patients in the group without immune-related overt TD (Overt_TD), the patients in the Overt_TD group had a longer PFS (mPFS: 12.4 vs. 7.3 months, P = 0.015) and OS (mOS: 20.2 vs. 12.2 months, P = 0.001). The 60-, 90-, and 120-day landmark analysis further confirmed that immune-related TD was significantly associated with the improvement of PFS and OS. Multivariate Cox regression analysis indicated that immune-related TD was an independent prognostic factor for PFS ( P = 0.015) and OS ( P = 0.004). Immune-related TD is a very common immune-related adverse event. It is safe and manageable and has potential prognostic value for patients with advanced ESCC treated with PD-1 inhibitors.
Treatment of RET/ALK comutated advanced lung large cell neuroendocrine carcinoma: a case report and literature review.
Luo Y, Li D, Yang Q … +2 more , Dong Y, Chen W
Anticancer Drugs · 2025 Jul · PMID 40112204 · Publisher ↗
The prognosis of advanced lung large-cell neuroendocrine carcinoma is poor, and the efficacy of targeted therapy is still being explored. A case of RET fusion mutation combined with ALK rearrangement positive advanced lu...
The prognosis of advanced lung large-cell neuroendocrine carcinoma is poor, and the efficacy of targeted therapy is still being explored. A case of RET fusion mutation combined with ALK rearrangement positive advanced lung complex large cell neuroendocrine carcinoma was reported. The patient developed intrapulmonary and bone metastases 8 months after chemotherapy after lung cancer surgery, RET fusion mutations were detected by genetic testing, and intracranial progression occurred 1 year after pilatinib was applied. The comutation of RET and ALK was detected by genetic testing, and the pulmonary progression occurred 2 months after the application of aletinib, after being treated with pilatinib and aletinib, he progressed again in 9 months. We point out that large cell neuroendocrine carcinoma complex patients with RET gene mutation can benefit from targeted therapy, and when drug resistance is accompanied by ALK comutation, the patient can benefit from the treatment of the aletinib combined with pilatinib targeted therapy and the side effect is slight. At the same time, we further explore the resistance mechanism of targeted therapy in lung cancer.
Metformin-induced E6/E7 inhibition prevents HPV-positive cancer progression through p53 reactivation.
Zhang R, Hou F, Gan J … +7 more , Zhang L, Yang D, Yang F, Xia X, Chen Q, Bian C, Feng X
Anticancer Drugs · 2025 Jul · PMID 40100964 · Publisher ↗
The human papillomavirus (HPV) is implicated in multiple lethal cancers, although it is more sensitive to certain therapies than HPV-negative cancers. Therefore, the development of more targeted therapeutic strategies is...
The human papillomavirus (HPV) is implicated in multiple lethal cancers, although it is more sensitive to certain therapies than HPV-negative cancers. Therefore, the development of more targeted therapeutic strategies is imperative. The HPV oncogenes E6/E7 are ideal targets for HPV-positive cancer, but there are no clinical strategies that have been proven to effectively target E6/E7. Notably, metformin significantly inhibits E6/E7 expression; however, the underlying mechanism and therapeutic potential remain unclear, limiting its clinical translation. Cell Counting Kit-8, ethynyl-2'-deoxyuridine, and terminal-deoxynucleotidyl transferase-mediated Nick end labeling assays were conducted to evaluate the effects of metformin on cell viability, proliferation, and apoptosis. Quantitative real-time PCR, western blotting, and immunofluorescence assays were performed to determine changes in E6/E7 and p53 expression levels following metformin treatment. Patient-derived organoids and in-vivo xenograft models were constructed to evaluate the anticancer activity of metformin against HPV-positive cancer. Our research demonstrated enhanced sensitivity of HPV-positive cancer cells to metformin. Mechanistic studies have revealed that metformin exerts anticancer effects by inhibiting E6/E7 expression, which is associated with p53 reactivation. Furthermore, we substantiated the anticancer potential of metformin in HPV-positive patient-derived organoids and in-vivo tumor models. Our study focused on the mechanism underlying the enhanced responsiveness of HPV-positive cancer to metformin, highlighting the clinical potential of metformin as a targeted therapeutic strategy for HPV-positive cancer.
FV-429 suppresses cancer cell migration and invasion by EMT via the Hippo/YAP1 pathway in pancreatic cancer cells.
Wang Z, Pan X, Ma X … +4 more , Zhang Y, Gao Y, Guo Y, Zhou Y
Anticancer Drugs · 2025 Aug · PMID 40071582 · Publisher ↗
Pancreatic cancer is one of the most common malignant tumors of the digestive system, with the majority of patients not succumbing to the primary tumor but rather to metastasis. Epithelial-mesenchymal transition (EMT) is...
Pancreatic cancer is one of the most common malignant tumors of the digestive system, with the majority of patients not succumbing to the primary tumor but rather to metastasis. Epithelial-mesenchymal transition (EMT) is abnormally activated in numerous cancers, whereby it promotes tumor cell migration and invasion. Yes-associated protein 1 (YAP1) is commonly overexpressed in various cancer types and plays an oncogenic role. We demonstrated that FV-429, a derivative of the natural flavonoid wogonin, inhibited the invasion and metastasis of pancreatic cancer cells by modulating EMT-related proteins. FV-429 enhances the expression of p-LATS1, thereby promoting the conversion of YAP1 to p-YAP1. Meanwhile, it suppresses the nuclear translocation of YAP1, thereby affecting the expression of E-cadherin and snail1, which, in turn, impacts the EMT. The Hippo-signaling pathway inhibitor TDI-011536 was used to validate these results. In vivo , a mouse model of pancreatic cancer lung metastasis was established using PANC02 cells to validate the antimetastatic effect of FV-429, which confirmed its action through the Hippo/YAP1 pathway. In addition, FV-429 demonstrated high safety and low toxicity. In conclusion, we demonstrated that FV-429 inhibits migration, invasion, and metastasis of human pancreatic cancer cells by affecting the Hippo/YAP1 pathway, suggesting that FV-429 has the potential to be a novel therapeutic agent for pancreatic cancer.
GZ17-6.02 interacts with carboplatin and etoposide to kill neuroblastoma cells.
Booth MR, Booth L, Roberts JL … +2 more , West C, Dent P
Anticancer Drugs · 2025 Jul · PMID 40067790 · Publisher ↗
The biology of GZ17-6.02 alone and more so in combination with either of the standard-of-care agents etoposide or carboplatin killed MYCN overexpressing neuroblastoma (NB) cells is unknown. The methods involved in this s...
The biology of GZ17-6.02 alone and more so in combination with either of the standard-of-care agents etoposide or carboplatin killed MYCN overexpressing neuroblastoma (NB) cells is unknown. The methods involved in this study are in-cell immunoblotting, trypan blue exclusion, plasmid and siRNA transfection, assessment of autophagy using a plasmid expressing LC3-GFP-RFP. GZ17-6.02 (602) comprises, by mass, a ratio of curcumin (1.0), harmine (1.3), and isovanillin (7.7). In tumors dosed with 602, the ratio becomes curcumin (1.0), harmine (16), and isovanillin (6.1) (602NR). GZ17-6.02 activated ATM, AMPK, ULK1, ATG13, and PERK and inactivated ERBB1, ERBB2, ERBB3, ERBB4, AKT, mTORC1, mTORC2, SRC, NFκB, YAP, and eIF2α. 602 enhanced autophagosome formation and autophagic flux that was amplified when it was combined with etoposide or carboplatin. Compared with 602, 602NR caused significantly greater autophagosome formation that was also amplified when in combination with chemotherapy and which was reduced ~40% by knockdown of ATM or AMPKα and abolished by knockdown of Beclin1 or ATG5. Knockdown of ATM or AMPKα significantly reduced tumor cell death caused by 602 of 602NR, whereas endoplasmic reticulum stress (eIF2α) and macroautophagy (Beclin1, ATG5) were more effective at maintaining tumor cell survival. Combined knockdown of Beclin1 and the death receptor CD95 almost abolished the antitumor actions of 602 and 602NR. 602, and more so 602NR, kills MYCN NB cells and interacts with standard-of-care chemotherapeutics to cause further killing via autophagy and death receptor signaling.
Efficacy of disitamab vedotin (RC48) for previously treated human epidermal growth factor receptor 2-positive breast cancer with symptomatic brain metastases: a case report and review of the literature.
Yang C, Zhang C, Huang Y … +7 more , Zhu X, Jiang J, Zeng Y, Zhang H, Li L, Liu Y, Li Y
Anticancer Drugs · 2025 Jun · PMID 40063535 · Publisher ↗
Local radiotherapy or surgery is the standard of care for treating brain metastases among patients with breast cancer. However, affected by tumor subtype, more than 50% of human epidermal growth factor receptor 2 (HER2)-...
Local radiotherapy or surgery is the standard of care for treating brain metastases among patients with breast cancer. However, affected by tumor subtype, more than 50% of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases will still develop local recurrence or new brain lesions within 1 year after radiotherapy. As systemic therapies demonstrate higher and clinically relevant levels of intracranial activity and longer survival, there is limited evidence to guide how to weigh the options of radiotherapy versus systemic therapy (and deferral of radiation) in patients with progressive brain metastases, particularly those that are symptomatic. This study presents a case of progressive symptomatic HER2-positive brain metastases in a patient previously treated with whole brain radiotherapy and various targeted therapies. Due to limited access to novel HER2-targeted drugs, a new antibody-drug conjugate drug, disitamab vedotin (RC48) monotherapy, was chosen for postprogression treatment. The patient experienced rapid relief of neurological symptoms, partial regression of the brain tumor, and sustained disease remission for over 12 months without any treatment-related toxicity, also avoided reirradiation exposure and potential neurocognitive decline. The treatment of brain metastasis has been a topic of ongoing discussion. Our experience may offer valuable insights into managing HER2-positive progressive symptomatic brain metastases.
Identification and validation of mitochondria-related LncRNA signatures as a novel prognostic model for glioma.
Deng K, Zhao W, Dai L … +2 more , Jing Z, Ma L
Anticancer Drugs · 2025 Apr · PMID 40053488 · Publisher ↗
A predictive model for long-term survival is needed, and mitochondrial dysfunction is a key feature of cancer metabolism, though its link to glioma is not well understood. The aim of this study was to identify the molecu...
A predictive model for long-term survival is needed, and mitochondrial dysfunction is a key feature of cancer metabolism, though its link to glioma is not well understood. The aim of this study was to identify the molecular characteristics associated with glioma prognosis and explore its potential function. We analyzed RNA-seq data from The Cancer Genome Atlas and identified differentially expressed mitochondrial long noncoding RNAs (lncRNAs) using R's 'limma' package. A prognostic model was developed using 10 selected lncRNAs and validated with Cox regression and least absolute shrinkage and selection operator algorithm. The model's efficacy was assessed using Kaplan-Meier and receiver operating characteristic curve analyses, and its correlation with immune cell profiles and drug sensitivity was explored. A 10-mitochondria-related LncRNA signature was generated. The median risk score values are used to classify glioma samples into low-risk and high-risk groups. In breast patients, the signature-based risk score demonstrated a more potent ability to predict survival than conventional clinicopathological features. Furthermore, we noted a substantial disparity in the number of immune cells, including B cells, CD8 + T cells, and macrophages, between the two groups. In addition, the high-risk group exhibited lower half-maximal inhibitory concentration values for specific chemotherapy medications, including bortezomib, luminespib, rapamycin, and 5-fluorouracil. Our study elucidates the diagnostic and prognostic value of mitochondria-related-lncRNAs in the promotion, suppression, and treatment of glioma.
Thrombospondin-2 induces M2 macrophage polarization through fatty acid metabolism to drive lung adenocarcinoma proliferation.
Weng M, Zhu X
Anticancer Drugs · 2025 Jul · PMID 40053399 · Publisher ↗
Tumor-associated macrophages play a critical role in regulating the progression of lung adenocarcinoma (LUAD). Platelet-derived protein thrombospondin-2 (THBS2) has been identified as a tumor marker and is known to be ov...
Tumor-associated macrophages play a critical role in regulating the progression of lung adenocarcinoma (LUAD). Platelet-derived protein thrombospondin-2 (THBS2) has been identified as a tumor marker and is known to be overexpressed in LUAD. However, the specific role of THBS2 in M2 macrophage polarization within LUAD remains unclear. We conducted bioinformatics analyses to assess the clinical significance of THBS2 expression in LUAD, which was subsequently validated using quantitative PCR. We examined the relationship between THBS2 expression and M2 macrophage infiltration. A coculture system of LUAD cells and M0 macrophages was established to investigate the influence of THBS2 on macrophage infiltration and polarization through immunofluorescence and ELISA. We explored the impact of THBS2 on fatty acid metabolism (FAM) using oil red O staining and relevant kits and elucidated the role of THBS2 in regulating M2 macrophage polarization and LUAD proliferation through cell counting kit-8 (CCK-8) and colony formation assays. Western blot was employed to assess expression changes of Bax and Bcl-2. THBS2 was highly expressed in LUAD and was associated with poor prognosis in patients. In-vitro experiments demonstrated that silencing THBS2 significantly inhibited macrophage infiltration and polarization. THBS2 primarily activated FAM pathways, inducing M2 macrophage polarization and promoting LUAD cell proliferation. THBS2 enhanced LUAD proliferation by regulating FAM to induce M2 macrophage polarization. These findings provide a theoretical basis for targeting THBS2 as a novel therapeutic strategy in LUAD.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe