Anti-cancer Drugs[JOURNAL]
Sun
200 papers
WDR62 mediates MAPK/ERK pathway to stimulate DNA damage repair and attenuate cisplatin sensitivity in lung adenocarcinoma.
Li X, Guo Y, Qi Z … +1 more , Zheng Y
Anticancer Drugs · 2025 Apr · PMID 39808528 · Publisher ↗
Chemotherapy resistance has long stood in the way of therapeutic advancement for lung cancer patients, the malignant tumor with the highest incidence and fatality rate in the world. Patients with lung adenocarcinoma (LUA...
Chemotherapy resistance has long stood in the way of therapeutic advancement for lung cancer patients, the malignant tumor with the highest incidence and fatality rate in the world. Patients with lung adenocarcinoma (LUAD) now have a dismal prognosis due to the development of cisplatin (DDP) resistance, forcing them to use more costly second-line therapies. Therefore, overcoming resistance and enhancing patient outcomes can be achieved by comprehending the regulatory mechanisms of DDP resistance in LUAD. WD repeat domain 62 (WDR62) expression in LUAD tissues and in DDP-resistant or sensitive LUAD patients was analyzed bioinformatically, and a K-M plot was utilized to assess survival status. Real-time quantitative PCR was employed for WDR62 expression detection, cell-counting kit-8 assay for half maximal inhibitory concentration determination, flow cytometry for cell apoptosis detection, immunofluorescence for γ-H2AX expression analysis, and western blot for nonhomologous end joining repair and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway-related protein expression analysis. Poor prognosis was linked to WDR62, which was overexpressed in LUAD tissues and cells. Compared to sensitive cells, DDP-resistant cells had increased WDR62 expression. WDR62 knockdown may enhance DDP-induced cell apoptosis while reducing cell proliferation and DNA damage repair. Functional investigations verified that overexpressed WDR62's encouraging impact on DNA damage repair in A549/DDP cells could be reversed by MAPK inhibitors, increasing the cells' susceptibility to DDP. LUAD cells became less sensitive to DDP when WDR62 activated the MAPK/ERK pathway, which promoted DNA damage repair, indicating that DDP resistance might be reversed by treating LUAD with inhibitors of the MAPK pathway.
Clinical efficacy of pyrotinib combined with chemotherapy for neoadjuvant treatment in HER2-positive breast cancer: a single-center study.
Wei B, Yan H, Li F … +1 more , Shen J
Anticancer Drugs · 2025 Apr · PMID 39808527 · Publisher ↗
This study aimed to evaluate the efficacy of pyrotinib, an orally administered small molecule tyrosine kinase inhibitor, combined with neoadjuvant chemotherapy in treating patients with human epidermal growth factor rece...
This study aimed to evaluate the efficacy of pyrotinib, an orally administered small molecule tyrosine kinase inhibitor, combined with neoadjuvant chemotherapy in treating patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Pyrotinib works by inhibiting the HER2 signaling pathway, thereby preventing tumor cell growth. This single-arm clinical trial aimed to assess the total pathological complete response (tpCR; ypT0/is and ypN0) rate as the primary endpoint. A total of 27 patients were enrolled, each receiving 4-8 cycles of pyrotinib in combination with neoadjuvant chemotherapy. Pyrotinib combined with neoadjuvant chemotherapy demonstrated notable antitumor activity in patients with HER2-positive breast cancer. Among 26 patients, the tpCR rate was 26% (7/26), while the breast pathological complete response rate was 30% (8/26), indicating complete inhibition of the primary tumor in some cases. Notably, patients with HR-negative breast cancer demonstrated a higher tpCR rate compared with those with HR-positive breast cancer. The treatment regimen was well-tolerated. Diarrhea was the most common adverse event, occurring in 92.3% of patients, with 46.2% experiencing grade 3 or higher diarrhea. No severe adverse events or treatment-related fatalities were reported.
Berberine inhibits prostate cancer progression by inducing ferroptosis: evidence from network pharmacology.
Zou P, Li S, He Q … +1 more , Zheng C
Anticancer Drugs · 2025 Apr · PMID 39808208 · Publisher ↗
The uncertain ferroptosis-related role of berberine in prostate cancer was explored using network pharmacology methodology. Integration of ferroptosis targets in prostate cancer from the Genecard database and berberine t...
The uncertain ferroptosis-related role of berberine in prostate cancer was explored using network pharmacology methodology. Integration of ferroptosis targets in prostate cancer from the Genecard database and berberine targets from the Traditional Chinese Medicine Systems Pharmacology and SwissTargetPrediction databases revealed 17 common targets. Among these, 10 hub genes, including CCNB1 , CDK1 , AURKA , AR , CDC42 , ICAM1 , TYMS , NTRK1 , PTGS 2, and SCD , were identified. Enrichment analyses yielded 799 Gene Ontology terms and 23 Kyoto Encyclopedia of Genes and Genomes pathways associated with berberine-related targets. Molecular docking simulations indicated berberine's binding capacity to all hub genes. In-vitro studies on LNCaP and PC3 cells demonstrated berberine's inhibition of cell proliferation and significant downregulation of TYMS , CCNB1 , AURKA , CDK1 , and SCD in both cell lines. Berberine exhibited cell line-specific effects by reducing AR expression in LNCaP cells and suppressing ICAM1 in PC3 cells. Overall, berberine shows promise in inhibiting prostate cancer progression through modulation of ferroptosis-related genes, including TYMS , AR , CCNB1 , AURKA , CDK1 , ICAM1 , NTRK1 , SCD , and CDC42 .
Transformation of lung adenocarcinoma to small cell lung cancer following osimertinib treatment: a case report and literature review.
Kuang L, Wang P, Zhou L … +1 more , Li Y
Anticancer Drugs · 2025 Mar · PMID 39792045 · Full text
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) effectively treat EGFR-mutant lung adenocarcinoma, demonstrating initial efficacy but eventually leading to acquired resistance. Small cell transf...
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) effectively treat EGFR-mutant lung adenocarcinoma, demonstrating initial efficacy but eventually leading to acquired resistance. Small cell transformation is a rare resistance mechanism to EGFR-TKIs in lung adenocarcinoma, which can complicate clinical diagnosis and treatment. We present a patient with lung adenocarcinoma who underwent a prior pneumonectomy and adjuvant chemotherapy and was treated with osimertinib after the recurrence of lung cancer. Small cell transformation occurred approximately 20 months after starting osimertinib treatment. After this transformation, the patient underwent lung radiotherapy and cisplatin-etoposide chemotherapy, which stabilized the disease. Following the confirmation of small cell lung cancer (SCLC) via thyroid puncture, treatments with irinotecan, irinotecan plus atezolizumab, thyroid radiotherapy, adrenal radiotherapy, and head radiotherapy were sequentially administered, yet the disease continued to progress. The patient succumbed to the disease in May 2023 because of progression and organ failure, with an overall survival of 52.7 months, including 16 months post small cell transformation. This case highlights the possibility of osimertinib causing lung adenocarcinoma to transform into SCLC and underscores rebiopsies' importance in identifying resistance mechanisms to EGFR-TKIs. Increased levels of neuron-specific enolase and pro-gastrin releasing peptide can signal early transformation into SCLC.
Research on the mechanism of eugenol in the treatment of liver cancer based on network pharmacology, molecular docking technology, and in vitro experiments.
Liu K, Jiang J, Yu Z … +3 more , Wang Y, Wang M, Zhu H
Anticancer Drugs · 2025 Mar · PMID 39786976 · Publisher ↗
Eugenol, a phenolic natural product with diverse pharmacological activities, remains unexplored in liver cancer. Using network pharmacology, we investigated eugenol's therapeutic mechanisms in liver cancer. We obtained e...
Eugenol, a phenolic natural product with diverse pharmacological activities, remains unexplored in liver cancer. Using network pharmacology, we investigated eugenol's therapeutic mechanisms in liver cancer. We obtained eugenol's molecular structure from PubChem and screened its targets using similarity ensemble approach in Swiss Target Predictiondatabases. Overlapping genes with liver cancer-related genes from GeneCards were identified. Protein-protein interaction networks, Gene Ontology annotations, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted. A target-pathway network revealed eugenol's interaction with 122 liver cancer-related genes. Molecular docking confirmed eugenol's high affinity for mitochondrial nicotinamide adenine dinucleotide, reduced form (NADH) dehydrogenase 1 (MT-ND1), AKT1, NDUFB7, and NADH dehydrogenase (complex I) subunit S3 (NDUFS3). Expression levels of these targets in normal liver and liver cancer tissues were examined using GEPIA2 and HPA databases. The CCK-8 assay and colony formation assay demonstrated that eugenol significantly inhibited the proliferation of hepatocellular carcinoma cells. Western blot analysis confirmed that eugenol upregulated MT-ND1 while downregulating the expression of targets such as AKT1, NDUFB7, and NDUFS3. Furthermore, it was found that eugenol could influence the expression of the AKT1 target through the AKT/p70 S6K pathway. This study provides new insights into the potential mechanisms of eugenol in liver cancer and offers novel perspectives for network-based liver cancer research.
Comprehensive analysis of DNA methylation and gene expression to identify tumor suppressor genes reactivated by MLN4924 in acute myeloid leukemia.
Guo Y, Jian J, Tang X … +2 more , Zhao L, Liu B
Anticancer Drugs · 2025 Mar · PMID 39786970 · Publisher ↗
This study investigated whether the neddylation inhibitor MLN4924 induces aberrant DNA methylation patterns in acute myeloid leukemia and contributes to the reactivation of tumor suppressor genes. DNA methylation profile...
This study investigated whether the neddylation inhibitor MLN4924 induces aberrant DNA methylation patterns in acute myeloid leukemia and contributes to the reactivation of tumor suppressor genes. DNA methylation profiles of Kasumi-1 and KU812 acute myeloid leukemia cell lines before and after MLN4924 treatment were generated using the 850K Methylation BeadChip. RNA sequencing was used to obtain transcriptomic profiles of Kasumi-1 cells. Target genes were identified through a combined analysis of methylation and transcriptome data. Methylation-specific PCR and quantitative PCR validated the changes in methylation and expression. Prognostic analysis of target genes was performed using databases, and Pearson correlation was used to examine the relationship between methylation and expression levels. In Kasumi-1 and KU812 cells, 301 and 469 differentially methylated sites, respectively, were identified. A total of 4310 differential expression genes were detected in Kasumi-1. Combined analysis revealed that TRIM58 exhibited significant demethylation and upregulation after MLN4924 treatment, as confirmed by quantitative and methylation-specific PCR. Furthermore, database analysis revealed that both down-expression and promoter hypermethylation of TRIM58 were correlated with poor prognosis in acute myeloid leukemia. A negative correlation was observed between TRIM58 methylation and expression levels. This study suggests that MLN4924 alters DNA methylation patterns in acute myeloid leukemia and reactivates TRIM58, a potential tumor suppressor gene, through demethylation.
Stereotactic body radiotherapy and poly (ADP-ribose) polymerase inhibitors in ovarian cancer: a knowledge and attitudes survey in collaboration with the Italian Association of Radiation Oncology (AIRO) and Multicenter Italian Trials in Ovarian Cancer (MITO) groups.
Macchia G, Pezzulla D, Russo D … +10 more , Campitelli M, Lucci S, Fanelli M, Deodato F, Fagotti A, Gambacorta MA, Savarese A, Pignata S, Aristei C, Ferrandina G
Anticancer Drugs · 2025 Mar · PMID 39784120 · Publisher ↗
The aim of this study was to present a nationwide survey on the specialist's attitudes towards stereotactic body radiotherapy (SBRT) combined with poly (ADP-ribose) polymerase inhibitors (PARPi) with oligometastatic/olig...
The aim of this study was to present a nationwide survey on the specialist's attitudes towards stereotactic body radiotherapy (SBRT) combined with poly (ADP-ribose) polymerase inhibitors (PARPi) with oligometastatic/oligoprogressive/oligorecurrent ovarian cancer (oMPR-OC) patients. The 19-item questionnaire was developed by specialists and distributed online. Replies were stratified by categories and analyzed using descriptive statistics. Respondents ( N = 100) were radiation oncologists (57%), medical oncologists (32%), and gynecologic oncologists (11%). Fifty-four percent of respondents considered medical oncologists as the primary oncologists for oMPR-OC, while 23% preferred radiation oncologists and 15% favored gynecologic oncologists. Seventy-three percent discuss these cases in the Multidisciplinary Tumor Board, while 15, 6, and 2% send the patients straight to SBRT, surgery, or chemotherapy, respectively. Seventy-four percent of the experts interviewed were treated with SBRT less than 10 oMPR-OC patients. Concomitant treatment was highly heterogeneous, but it had little to no reported side effects. A significant variation in how PARPi is managed during SBRT was found: 34% do not interrupt the administration, while 52% pause and restart it later. Forty-three percent of respondents believe that the PARPi dosage should not be reduced when administered concurrently with SBRT. Sixty-nine percent of respondents believe that the SBRT dose should not be decreased while receiving PARPi if the constraints are met. The majority of respondents (40%) favored expert consensus for enhancing the clinical management of oMPR-OC, while 34% preferred clinical guidelines. A lack of or low toxicity with the combination of PARPi and SBRT was perceived, and a significant degree of heterogeneity concerning clinical protocols for their combination. Moreover, it emphasizes the low number of patients who have received this treatment approach nationwide.
Dual inhibition of TYK2 and PD-L1 boosts immune response in triple negative breast cancer.
Xiang H, Tu B, Feng X … +2 more , Chen L, Huang Y
Anticancer Drugs · 2025 Apr · PMID 39774369 · Full text
Recent studies have shown that Janus Kinase inhibitors can enhance the tumor therapeutic effect of immune checkpoint inhibitors. However, it remains to be studied whether TYK2 selective inhibitors can enhance the therape...
Recent studies have shown that Janus Kinase inhibitors can enhance the tumor therapeutic effect of immune checkpoint inhibitors. However, it remains to be studied whether TYK2 selective inhibitors can enhance the therapeutic effect of small molecule PD-L1 inhibitors in triple-negative breast cancer (TNBC). We verified the efficacy of the combination of the selective TYK2 inhibitor Deucravacitinib and the small molecule inhibitor of PD-L1, INCB086550, in two TNBC animal models: a syngeneic mouse model (4T1 with humanized PD-L1) and a peripheral blood mononuclear cell (PBMC)-humanized model (MDA-MB-231). Following that, we explored the regulation of immune cell activity in tumors by the combined treatment using flow cytometry. Finally, we validated the expression of genes related to the regulated immune cells through reverse transcription-PCR. Both animal models demonstrated that the addition of a TYK2 inhibitor to a PD-L1 inhibitor significantly enhanced the antitumor capabilities of mice with good safety profiles. The combined therapy significantly elevated the counts of T, B, and natural killer cells while concurrently diminishing myeloid-derived suppressor cells in the syngeneic model. Similarly, in the PBMC-humanized model, this therapy markedly augmented progenitor-like and proliferative precursor-like CD8 T cells, while effectively diminishing exhausted and terminally differentiated CD8 T cell populations. This enhanced antitumor effect is associated with the modulation of antitumor immune-related gene expression by the combined therapy. The combination of TYK2 inhibitors and immune checkpoint inhibitors is a potentially effective strategy for treating TNBC.
Albumin-based nanocarriers loaded with novel Zn(II)-thiosemicarbazone compounds chart a new path for precision breast cancer therapy.
Danişman-Kalindemirtaş F, Özerkan D, Kariper İA … +3 more , Erdemir Cilasun G, Ülküseven B, Erdem-Kuruca S
Anticancer Drugs · 2025 Mar · PMID 39774332 · Publisher ↗
This study explores the therapeutic potential of albumin-bound Zn(II)-thiosemicarbazone compounds (Alb-ZnTcA, Alb-ZnTcB) against breast cancer cells. Previous research indicates that these compounds hinder cancer cell pr...
This study explores the therapeutic potential of albumin-bound Zn(II)-thiosemicarbazone compounds (Alb-ZnTcA, Alb-ZnTcB) against breast cancer cells. Previous research indicates that these compounds hinder cancer cell proliferation by blocking DNA synthesis, promoting oxidative stress to induce apoptosis, and disrupting the cell cycle to inhibit cellular division. This study focuses on the loading and characterization of these potentially chemically unstable compounds on bovine serum albumin-based nanocarriers. Accordingly, unlike previous studies using albumin nanoparticles, in this study, ultraviolet light was used to precisely bind the therapeutic agent to albumin during the integration of thiosemicarbazones, achieving controlled nanoparticle size to control nanoparticle size. The mean diameter of Alb-ZnTcA nanoparticles was 32 nm, while Alb-ZnTcB exhibited an average diameter of 43 nm. Notably, Alb-ZnTcA displayed the highest cytotoxicity toward breast cancer cells, suggesting an optimal size for cellular uptake. Additionally, albumin-bound compounds showed enhanced cytotoxicity at lower concentrations, potentially minimizing adverse side effects. Apoptosis analysis indicated that both Alb-ZnTcA and Alb-ZnTcB induce cell death predominantly through apoptosis, effectively preventing the uncontrolled proliferation of cancer cells. These findings demonstrate the potential of Zn(II)-thiosemicarbazone compounds loaded on albumin-based nanocarriers for breast cancer treatment. The increased potency of Alb-ZnTcA and Alb-ZnTcB compared to free compounds, along with their ability to activate apoptotic signaling pathways in MCF-7 breast cancer cells, highlights a promising approach for future cancer therapies. This study suggests that albumin-bound Zn(II)-thiosemicarbazone compounds could offer a targeted and effective strategy in breast cancer treatment, leveraging the advantages of nanocarrier-based delivery systems.
WISP1 inhibition of YAP phosphorylation drives breast cancer growth and chemoresistance via TEAD4 activation.
Dong T, Liu L, You Y … +4 more , Liu J, Wang F, Li S, Yu Z
Anticancer Drugs · 2025 Mar · PMID 39774151 · Full text
Wnt1-inducible signaling pathway protein 1 (WISP1) promotes breast cancer. The Hippo signaling pathway demonstrates a potential connection with WISP1, necessitating an exploration of their interaction. This study hypothe...
Wnt1-inducible signaling pathway protein 1 (WISP1) promotes breast cancer. The Hippo signaling pathway demonstrates a potential connection with WISP1, necessitating an exploration of their interaction. This study hypothesized that WISP1 boosts breast cancer by modulating the Hippo signaling pathway. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to analyze WISP1 expression and Hippo signaling in breast cancer patients. WISP1, yes-associated protein (YAP), and domain family member 4 (TEAD4) were overexpressed or silenced in breast cancer cells. Epithelial-mesenchymal transition (EMT), and chemoresistance of breast cancer cells were evaluated. Immunofluorescence, PCR, immunoprecipitation, and western blot were used to detect the expression of WISP1 and key Hippo signaling factors and their interactions. Enrichment analysis indicated activation of WISP1 and Hippo signaling pathway and correlated with a worse prognosis in breast cancer. WISP1 overexpression facilitated EMT and chemotherapy resistance in breast cancer. Importantly, overexpression of WISP1 promoted YAP's nuclear translocation. TEAD4 expression in YAP precipitates from nuclear of WISP1-overexpressing MCF-7 cells increased. The promoting effect of WISP1 on breast cancer was counteracted by silencing YAP or TEAD4. Moreover, in WISP1 small interfering RNA-transfected MCF-7 cells, p-YAP expression increased, while interaction between YAP and TEAD4 decreased. WISP1 silencing led to ubiquitin increase and TEAD reduction in the p-YAP precipitates. In conclusion, WISP1 promotes YAP nuclear translocation and binding with TEAD4 by inhibiting YAP phosphorylation, reducing ubiquitin recruitment, and participating in transcriptional regulation in breast cancer.
A dual thermo/pH-sensitive hydrogel as 5-Fluorouracil carrier for breast cancer treatment.
Luo K, Hu W
Anticancer Drugs · 2025 Mar · PMID 39773648 · Full text
Intelligent hydrogels are promising in constructing scaffolds for the controlled delivery of drugs. Here, a dual thermo- and pH-responsive hydrogel called PCG [poly ( N -isopropyl acrylamide-co-itaconic acid)/chitosan/gl...
Intelligent hydrogels are promising in constructing scaffolds for the controlled delivery of drugs. Here, a dual thermo- and pH-responsive hydrogel called PCG [poly ( N -isopropyl acrylamide-co-itaconic acid)/chitosan/glycerophosphate (PNI/CS/GP)] was established as the carrier of 5-fluorouracil (5-FU) for triple-negative breast cancer (TNBC) treatment. The PCG hydrogel was fabricated by blending synthesized [poly ( N -isopropyl acrylamide-co-itaconic acid), pNIAAm-co-IA, PNI] with CS in the presence of GP as a crosslinking agent. The interaction between PCG hydrogel compositions was characterized by Fourier transforms infrared, NMR spectroscopy, and scanning electron microscopy. The PCG hydrogel presented an interconnected and porous structure with similar pore size, rapid swelling/deswelling rate in response to both temperature and pH change, and biocompatibility, upon which it was proposed as a great drug carrier. 5-FU had a dual thermo- and pH-responsive controlled release behavior from the PCG hydrogel and displayed an accelerated release rate in an acidic pH environment than in a neutral pH condition. The application of 5-FU-loaded PCG hydrogel exhibited a more promoted anticancer activity than 5-FU against the growth of TNBC cells both in vitro and in vivo . The outcomes suggested that the PCG hydrogel could be an excellent platform for local drug-delivery systems in the clinical therapy of TNBC.
Paeoniflorin sensitizes imatinib mesylate-resistant chronic myeloid leukemia cells via the inhibition of Cyr61 production.
Song Y, Luo L, Lin Z … +4 more , Zhang T, Li Z, Cao Y, Zhu X
Anticancer Drugs · 2025 Mar · PMID 39773616 · Publisher ↗
Imatinib mesylate (IM) is a first-line therapy for chronic myeloid leukemia (CML) and exhibits good therapeutic effects, but not in all patients with CML owing to drug resistance. Our previous study showed that Cyr61 pla...
Imatinib mesylate (IM) is a first-line therapy for chronic myeloid leukemia (CML) and exhibits good therapeutic effects, but not in all patients with CML owing to drug resistance. Our previous study showed that Cyr61 plays a key role in IM resistance in CML cells. Paeoniflorin (PF) is a bioactive compound isolated from the traditional Chinese medicine Paeonia lactiflora Pall that displays anticancer activity. Little is, however, known regarding the role of PF in IM-resistant CML cells. This study aimed to evaluate whether PF could decrease Cyr61 production and improve IM-resistant CML cell sensitivity to IM and to investigate the underlying mechanisms. CML cell lines (K562 and KCL22) and IM-resistant cell lines (K562G and KCL22R) were used as CML study models. Cyr61 expression was assessed in both parental and IM-resistant CML cells by western blotting, real-time quantitative PCR , and ELISA. Lentiviral vectors were used to induce the knockdown of Cyr61 expression, followed by a comprehensive evaluation of cell proliferation and apoptosis. The results showed that PF decreased the production of Cyr61 in the presence of IM by inhibiting extracellular regulated protein kinases 1/2 activation. PF significantly decreased the IC50 value of IM and increased IM-induced apoptosis of IM-resistant CML cells. Importantly, PF also improved the sensitivity of CML cells to bosutinib and dasatinib via inhibition of Cyr61 production. In conclusion, we report for the first time that PF may effectively improve the sensitivity of IM-resistant CML cells to IM, bosutinib, and dasatinib, at least in part, by subsequently downregulating Cyr61.
High CXCL8 expression predicting poor prognosis in triple-negative breast cancer.
Tang S, Zhang Y, Song L … +2 more , Hui K, Jiang X
Anticancer Drugs · 2025 Mar · PMID 39761194 · Full text
Triple-negative breast cancer (TNBC) is highly prone to early relapse and metastasis following standard treatment. CXCL8 is a key factor in tumor invasion and metastasis, but its role in TNBC prognosis and clinicopatholo...
Triple-negative breast cancer (TNBC) is highly prone to early relapse and metastasis following standard treatment. CXCL8 is a key factor in tumor invasion and metastasis, but its role in TNBC prognosis and clinicopathological correlations remains poorly understood. This study investigated CXCL8 expression and its clinical significance in TNBC to develop a prognostic nomogram for guiding intensive treatment and follow-up strategies. Public datasets from the gene expression omnibus public datasets platform were analyzed to assess CXCL8 expression. Additionally, paraffin-embedded TNBC specimens collected from our hospital were examined using immunohistochemistry to explore the relationship between CXCL8 expression and clinicopathological features. Survival analysis was performed to evaluate whether CXCL8 serves as an unfavorable prognostic biomarker for TNBC patients. Univariate Cox regression analysis was conducted to identify prognostic factors. Based on these findings, a nomogram was developed to predict TNBC progression risk. CXCL8 expression was significantly higher in TNBC tissues than in adjacent normal tissues ( P < 0.05). Among 122 TNBC patients, 46 were CXCL8-positive and 76 were CXCL8-negative. CXCL8 expression was significantly associated with N stage ( P < 0.05). Progression-free survival (PFS) was markedly shorter in the CXCL8-positive group compared with the CXCL8-negative group ( P < 0.001). Univariate Cox regression identified N1-3, M1, and CXCL8 positivity as significant risk factors for disease progression. A nomogram incorporating these variables (N, M, and CXCL8) was constructed to predict PFS. Time-dependent receiver operating characteristic curve analysis at 12-, 36-, and 48-month demonstrated strong predictive performance, with area under the curve values of 0.857, 0.839, and 0.795, respectively. CXCL8 is highly expressed in TNBC and promotes lymphatic metastasis, serving as an unfavorable prognostic factor. The developed nomogram offers a valuable tool for guiding personalized treatment and follow-up strategies in TNBC patients.
The impact of bevacizumab intraperitoneal perfusion combined with paclitaxel and platinum-based chemotherapy on serum stromal-derived factor-1α (SDF-1α) and chemokine ligand 5 (CXCL-5) levels in patients with ovarian cancer after tumor cell debulking surgery.
Wang L, Ma S, Su H … +2 more , Nie D, Wang L
Anticancer Drugs · 2025 Mar · PMID 39757759 · Full text
The aim of this study is to investigate the impact of bevacizumab intraperitoneal perfusion combined with paclitaxel and platinum-based chemotherapy on serum stromal-derived factor-1α (SDF-1α) and chemokine ligand 5 (CXC...
The aim of this study is to investigate the impact of bevacizumab intraperitoneal perfusion combined with paclitaxel and platinum-based chemotherapy on serum stromal-derived factor-1α (SDF-1α) and chemokine ligand 5 (CXCL-5) levels in patients with ovarian cancer after tumor cell debulking surgery. This clinical study was conducted on a cohort of 89 ovarian cancer patients who underwent tumor debulking surgery at our hospital from February 2020 to February 2021. The patients were divided into two groups using a random number table: the control group ( n = 44) received postoperative treatment with paclitaxel and platinum-based chemotherapy, while the research group ( n = 45) received additional treatment with intraperitoneal perfusion of bevacizumab in addition to the control group's treatment regimen. The analysis included an assessment of the clinical efficacy of both groups, changes in tumor biomarker levels before and after treatment, serum levels of SDF-1α and CXCL-5, T-lymphocyte subset levels, treatment-related adverse reactions, and a 2-year prognosis and survival assessment. The research group showed better performance compared to the control group in terms of disease remission rate (80.00% vs. 59.09%) and treatment effectiveness rate (95.56% vs. 75.00%) ( P < 0.05). Before treatment, the levels of tumor biomarkers between the two groups were compared ( P > 0.05). After treatment, the levels of serum ferritin, carbohydrate antigen 125, carbohydrate antigen 199, and human epididymis protein 4 in both groups significantly decreased compared to before treatment, with the research group having lower levels ( P < 0.05). Before treatment, serum levels of SDF-1α and CXCL-5 between the two groups were compared ( P > 0.05). After treatment, however, the levels of SDF-1α and CXCL-5 significantly decreased compared to before treatment, with the research group having lower levels than the control group ( P < 0.05). Before treatment, there was no difference in T-lymphocyte levels between the two groups ( P > 0.05). In the control group, there was no significant change in T-lymphocyte levels before and after treatment ( P > 0.05). In the research group, however, after treatment, each indicator increased compared to before treatment, and posttreatment levels of all indicators were higher than those in the control group ( P < 0.05). The adverse reactions were compared between the two groups ( P > 0.05). The research group had a longer average survival time than the control group, with 1-year and 2-year survival rates higher than the control group ( P < 0.05). There was, however, no significant difference between the two groups in terms of local recurrence and metastasis ( P > 0.05). In conclusion, bevacizumab intraperitoneal perfusion combined with paclitaxel and platinum-based chemotherapy shows better clinical efficacy in the treatment of ovarian cancer after tumor cell debulking surgery. It can significantly reduce the levels of serum SDF-1α and CXCL-5 in patients, improve survival rates, and demonstrate good safety.
A rare EGFR exon 19 insertion mutation in metastatic lung adenocarcinoma: a favorable response to afatinib.
Seven İ, Köş FT, Tatli Doğan H … +5 more , Kişlal MH, Sekmek S, Karahan İ, Aktürk Esen S, Uncu D
Anticancer Drugs · 2025 Feb · PMID 39749551 · Publisher ↗
Epidermal growth factor receptor (EGFR) mutations like the common L858R and exon 19 deletions are well studied, but rarer mutations like exon 19 insertions have received less attention. This case report describes a patie...
Epidermal growth factor receptor (EGFR) mutations like the common L858R and exon 19 deletions are well studied, but rarer mutations like exon 19 insertions have received less attention. This case report describes a patient with this uncommon EGFR exon 19 insertion mutation in metastatic lung adenocarcinoma. A 51-year-old male nonsmoker with metastatic lung adenocarcinoma and a rare EGFR exon 19 insertion mutation experienced disease progression on initial carboplatin-pemetrexed chemotherapy. However, treatment with the second-generation tyrosine kinase inhibitor afatinib led to a partial response, with significant regression of the primary tumor and bone metastases. This case highlights the favorable clinical response to afatinib treatment in a patient with metastatic nonsmall cell lung cancer harboring a rare EGFR exon 19 insertion mutation.
Myositis associated with pembrolizumab presenting with myastheniform symptoms: two case reports.
Deveci Ş, Uzun M, Özçelik P … +2 more , Tümer Doğukan SS, Matur Z
Anticancer Drugs · 2025 Feb · PMID 39749550 · Publisher ↗
Immune checkpoint inhibitors (ICIs), such as pembrolizumab, have revolutionized cancer treatment by enhancing the immune system's response to malignancies. However, these therapies are associated with immune-related adve...
Immune checkpoint inhibitors (ICIs), such as pembrolizumab, have revolutionized cancer treatment by enhancing the immune system's response to malignancies. However, these therapies are associated with immune-related adverse events (irAEs), including neuromuscular complications such as myasthenia gravis, myositis, and myocarditis. We describe two male patients, aged 67 and 68, with small cell and non-small cell lung cancers, who developed progressive neuromuscular symptoms, including ptosis, diplopia, and generalized weakness, after receiving pembrolizumab. Clinical, biochemical, imaging, and electrophysiological findings confirmed the diagnosis of myositis with myastheniform features, with one case also involving myocarditis. Both patients underwent treatments with intravenous immunoglobulin (IVIg), pyridostigmine, and corticosteroids. The first patient, despite aggressive treatment including plasma exchange and rituximab, succumbed to complications from aspiration pneumonia. The second patient showed partial response to pyridostigmine and IVIg but later died due to metastatic cancer progression. A literature review revealed 52 cases of pembrolizumab-associated myositis with myastheniform symptoms, emphasizing its high morbidity and the need for vigilant monitoring. Pembrolizumab-associated myositis with myastheniform symptoms, especially when accompanied by myocarditis, presents a significant clinical challenge with high mortality. Early recognition and aggressive management of these irAEs are crucial to improving outcomes in cancer patients receiving ICIs.
Inhibiting FGFR by toadflax reverses erlotinib resistance in nonsmall cell lung cancer.
Han B, Ma Y, Bao S … +7 more , Gao H, Gao Y, Guo Q, Li A, Li M, Yu R, Wang H
Anticancer Drugs · 2026 Jun · PMID 39724548 · Publisher ↗
This study aims to demonstrate the effect of toadflax (bufalin) on erlotinib resistance in nonsmall cell lung cancer (NSCLC) by inhibiting the fibroblast growth factor receptor (FGFR). The microfluidic mobility transfera...
This study aims to demonstrate the effect of toadflax (bufalin) on erlotinib resistance in nonsmall cell lung cancer (NSCLC) by inhibiting the fibroblast growth factor receptor (FGFR). The microfluidic mobility transferase and caliper mobility-shift assays were employed to detect the FGFR inhibition by bufalin and the binding reversibility. Further, the inhibitory effects of bufalin were determined in HCC827 and HCC827/ER cells in vitro , investigating relative FGFR overexpression by quantitative reverse transcriptase-PCR (RT-qPCR) and FGFR downstream proteins, that is, FGFR substrate 2 (FRS2), extracellular signal-regulated kinase (ERK), and S6 by western blot analysis. Finally, HCC827/ER-inoculated xenograft tumors were constructed to observe the effects of bufalin and bufalin + erlotinib intervention on tumor growth. Bufalin inhibited FGFR by reversibly binding to FGFR1. In addition, the western blot analysis indicated a significant reduction in the expression levels of FGFR, FRS2, ERK, and S6 proteins in HCC827 and HCC827/ER cells, increasing the expression levels of apoptotic caspase-3 and poly-(ADP-ribose) polymerase proteins. Bufalin + erlotinib combination significantly inhibited the apoptosis of HCC827/ER cells and subsequent tumor growth in vivo . In addition, FGFR overexpression significantly reversed the sensitivity of bufalin to HCC827/ER cells, promoting the value-addition of HCC827/ER cells. Further, bufalin + erlotinib significantly reduced the growth of erlotinib-resistant HCC827/ER tumors, induced apoptosis, and inhibited the expression of FGFR and p-ERK proteins. These findings indicated that bufalin could reverse the erlotinib resistance in NSCLC by inhibiting the FGFR expression.
Combination of anlotinib and sintilimab for the treatment of recurrent or metastatic head and neck squamous cell carcinoma: a single-arm prospective study.
Wang T, Wang J, Zhang Y … +3 more , Song Y, Xu G, Zhang B
Anticancer Drugs · 2025 Jan · PMID 39671265 · Full text
To investigate whether blocking both programmed cell death protein and vascular endothelial growth factor receptor could offer superior anticancer activity in these patients without compromising safety. In this study, pa...
To investigate whether blocking both programmed cell death protein and vascular endothelial growth factor receptor could offer superior anticancer activity in these patients without compromising safety. In this study, patients were administered oral anlotinib (12 mg/day) on days 1-14 and intravenous sintilimab (200 mg) on day 1 of a 3-weekly cycle. The primary endpoints included the objective response rate and disease control rate. The secondary endpoints included overall survival (OS) and safety. Ten eligible patients were enrolled between June 2019 and May 2022, and eight patients underwent radiographic assessments. The results showed an objective response rate of 50% (partial and complete response in four and zero patients, respectively) and a disease control rate of 100%; four patients demonstrated stable disease for at least 8 weeks. The median OS was 4.37 (in our study, the score was 7), and the OS rate at 12 months was 37.5%. The Kaplan-Meier survival curve showed that the group with high blood glucose levels had a significantly shorter duration of survival than those with normal blood glucose levels. Adverse events of grade 3 and higher occurred in 50% of patients, and the most common severe adverse events included tumor pain (50%), hypertension (37.5%), tumor hemorrhage (25%), and decreased appetite (25%). The combination of anlotinib and sintilimab showed promising efficacy in controlling tumor size. However, the disappointing OS rate suggests that anti-vascular endothelial growth factor receptor agents should be used cautiously after radical radiation therapy. The combination used in this study demonstrated a toxicity profile comparable to that of other agents used in this setting. These findings warrant further investigation into the potential clinical utility of this combination.
Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer.
Rinderle CH, Baker CV, Lagarde CB … +10 more , Nguyen K, Al-Ghadban S, Matossian MD, Hoang VT, Martin EC, Collins-Burow BM, Ali S, Drewry DH, Burow ME, Bunnell BA
Anticancer Drugs · 2025 Jan · PMID 39671264 · Full text
Triple-negative breast cancer (TNBC) is a highly invasive breast cancer subtype that is challenging to treat due to inherent heterogeneity and absence of estrogen, progesterone, and human epidermal growth factor 2 recept...
Triple-negative breast cancer (TNBC) is a highly invasive breast cancer subtype that is challenging to treat due to inherent heterogeneity and absence of estrogen, progesterone, and human epidermal growth factor 2 receptors. Kinase signaling networks drive cancer growth and development, and kinase inhibitors are promising anti-cancer strategies in diverse cancer subtypes. Kinase inhibitor screens are an efficient, valuable means of identifying compounds that suppress cancer cell growth in vitro , facilitating the identification of kinase vulnerabilities to target therapeutically. The Kinase Chemogenomic Set is a well-annotated library of 187 kinase inhibitor compounds that indexes 215 kinases of the 518 in the known human kinome representing various kinase networks and signaling pathways, several of which are understudied. Our screen revealed 14 kinase inhibitor compounds effectively inhibited TNBC cell growth and proliferation. Upon further testing, three compounds, THZ531, THZ1, and PFE-PKIS 29, had the most significant and consistent effects across a range of TNBC cell lines. These cyclin-dependent kinase (CDK)12/CDK13, CDK7, and phosphoinositide 3-kinase inhibitors, respectively, decreased metabolic activity in TNBC cell lines and promote a gene expression profile consistent with the reversal of the epithelial-to-mesenchymal transition, indicating these kinase networks potentially mediate metastatic behavior. These data identified novel kinase targets and kinase signaling pathways that drive metastasis in TNBC.
Refractory hypoglycemia is sensitive to octreotide therapy: is it triggered by sorafenib or hepatocellular carcinoma?
Çakmak M, Bal Ö, Kiraci M … +3 more , Topaloğlu O, Köş FT, Algin E
Anticancer Drugs · 2025 Feb · PMID 39625742 · Publisher ↗
Hypoglycemia is a medical emergency with a multitude of potential causes. Paraneoplastic hypoglycemia represents a rare cause of this condition. Hepatocellular carcinoma (HCC) can result in paraneoplastic hypoglycemia th...
Hypoglycemia is a medical emergency with a multitude of potential causes. Paraneoplastic hypoglycemia represents a rare cause of this condition. Hepatocellular carcinoma (HCC) can result in paraneoplastic hypoglycemia through extensive tumor infiltration and the presence of insulin-like growth factor 2 precursors. In this article, a patient whose persistent hypoglycemia did not improve despite long-term intravenous glucose and high-dose steroid treatment and who was successfully treated with octreotide is described. A 50-year-old male patient with a diagnosis of metastatic HCC was admitted to the emergency department due to symptomatic hypoglycemia. His blood glucose level was found to be 40 mg/dl and he was hospitalized in our clinic for treatment. The patient, who had been on sorafenib treatment for 2 weeks due to HCC, was started on intravenous dextrose for hypoglycemia and steroid, glucagon, and octreotide treatments, respectively. The patient's sorafenib treatment was discontinued and a second-line palliative chemotherapy was initiated. The patient responded dramatically to octreotide treatment and the need for intravenous glucose gradually decreased. Following approximately six weeks after hospitalization, the patient's requirement for intravenous glucose was no longer necessary. HCC and its treatment is a complex process involving the activation or inhibition of various mechanisms, and refractory hypoglycemia may rarely be seen in patients with HCC. But the cause of hypoglycemia may not always be identified. In cases where the cause is not understood, other treatment options for hypoglycemia, such as increasing caloric intake, intravenous glucose administration, high-dose steroids, glucagon, and octreotide, should be considered.
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