Anti-cancer Drugs[JOURNAL]
Sun
200 papers
D430-2307 inhibits breast cancer cell growth by dual induction of apoptosis and G0/G1 arrest via phosphatidylinositol 3-kinase/protein kinase B signaling.
Xu J, Ni S, Yang Y … +2 more , Sheng D, Liu Y
Anticancer Drugs · 2026 Mar · PMID 41858295 · Publisher ↗
D430-2307 is a novel small-molecule compound identified through virtual screening of the Chemdiv database that markedly inhibited the proliferation of both MCF-7 and MDA-MB-231 breast cancer cells. In the present study,...
D430-2307 is a novel small-molecule compound identified through virtual screening of the Chemdiv database that markedly inhibited the proliferation of both MCF-7 and MDA-MB-231 breast cancer cells. In the present study, the anticancer activity and underlying molecular mechanisms of D430-2307 were investigated. Thiazolyl blue, colony formation, wound healing, and transwell assays were performed to assess the effects of D430-2307 on breast cancer cell proliferation, migration, and invasion. To elucidate the underlying mechanisms, flow cytometry, Western blotting, and fluorescence staining were performed to analyze cell-cycle distribution, apoptosis, and intracellular reactive oxygen species (ROS) levels. In addition, network pharmacology, transcriptomics, and bioinformatics analyses were integrated to identify core targets and associated pathways, while molecular docking was performed to verify target-ligand interactions. The results demonstrated that D430-2307 significantly inhibited breast cancer cell proliferation, migration and invasion, induced G 0 /G 1 cell cycle arrest, downregulated CDK4/6 expression, and promoted apoptosis through modulation of the Bax/Bcl-2 ratio and activation of caspase-3/7 signaling. Furthermore, D430-2307 suppressed the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway via elevation of intracellular ROS levels. These findings suggest that D430-2307 exerts antitumor effects through ROS-mediated suppression of PI3K/AKT signaling, G 0 /G 1 cell cycle arrest, and apoptosis induction, providing a foundation for the development of novel anti-breast cancer therapeutics.
APG-1252 enhances the anticancer role of paclitaxel in non-small-cell lung cancer cells by suppressing the extracellular regulated protein kinases/myeloid cell leukemia 1 pathway.
Qian L, Guo Z, Cao X … +5 more , Zhu H, Xu J, Chen X, Zong D, He X
Anticancer Drugs · 2026 Jan · PMID 41608859 · Publisher ↗
The efficacy of paclitaxel (PTX), an important chemotherapy drug in non-small-cell lung cancer (NSCLC) cells, is limited by its resistance. APG-1252 has an inhibitory role in cancer and can inhibit myeloid cell leukemia...
The efficacy of paclitaxel (PTX), an important chemotherapy drug in non-small-cell lung cancer (NSCLC) cells, is limited by its resistance. APG-1252 has an inhibitory role in cancer and can inhibit myeloid cell leukemia 1 (MCL-1) to enhance chemotherapy drugs' antitumor effect. Therefore, this research further investigated whether APG-1252 could enhance the anticancer role of PTX by regulating MCL-1. NSCLC cells were treated with drugs. Cell viability was determined using the cell counting kit-8 assay. The cell apoptosis was examined using flow cytometry and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining. The abilities of cells to migrate, invade, and proliferate were examined using transwell and colony formation assays, as needed. The expression levels of extracellular regulated protein kinases (ERK), phosphorylated ERK (p-ERK), and MCL-1 were quantified by Western blot. APG-1252 and PTX decreased the NSCLC cells' viability. APG-1252 and PTX induced cell apoptosis and inhibited the cells from migrating, proliferating, and invading. APG-1252 and PTX suppressed the expression of p-ERK and MCL-1. Besides, APG-1252 enhanced the anticancer role of PTX in NSCLC cells. Ro 67-7476, a p-ERK agonist, had an opposite role to the combination of APG-1252 with PTX in NSCLC cells. Additionally, Ro 67-7476 abolished the anticancer role of the combination of APG-1252 with PTX in the biological functions of NSCLC cells. APG-1252 enhanced the anticancer role of PTX in NSCLC cells by suppressing the ERK/MCL-1 pathway. This work provided the theoretical basis for the APG-1252 application.
The good, the bad, and the manageable: real-world outcomes with CDK4/6 inhibitors.
Paulet A, Mancini S, Catalano M … +5 more , Shtembari K, De Angelis C, Petrioli R, Generali D, Roviello G
Anticancer Drugs · 2026 Jan · PMID 41601163 · Publisher ↗
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy represent the standard of care for hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC). While clinical tria...
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy represent the standard of care for hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC). While clinical trials established their efficacy, real-world evidence on safety, dose adjustments, and outcomes remains limited. We conducted a prospective observational study including patients with HR+/HER2- mBC treated with palbociclib, ribociclib, or abemaciclib across three oncology units between 2019 and 2024. Data on adverse events, dose modifications, progression-free survival (PFS), and overall survival (OS) were collected and analyzed. Adverse events were reported in 77.5% of patients. Neutropenia was the most frequent adverse event with palbociclib and ribociclib, while diarrhea and hepatic toxicity predominated with abemaciclib. Pulmonary toxicity occurred in 19.1% of abemaciclib-treated patients, often in those previously irradiated. Median PFS and OS were 26.4 and 31.1 months, respectively. The occurrence of grade 3-4 adverse events correlated with improved OS (37.1 vs. 23.0 months, P < 0.001). Dose reductions, required in more than 60% of patients, did not compromise efficacy; instead, they were associated with longer PFS and OS. Conversely, treatment discontinuation predicted worse outcomes. In real-world practice, CDK4/6i toxicities are frequent but manageable. Proactive toxicity management and timely dose adjustments are essential to sustain treatment benefit. Dose reductions may even improve outcomes, underscoring the value of individualized dosing strategies.
Dual checkpoint inhibition achieves successful treatment of diffuse bilateral lung metastasis in giant advanced liver cancer: a case report.
Xie TT, Chen W, Zeng ZH … +7 more , Luo JH, Wang Y, Peng XM, Lin MD, Song J, Xu M, Li Y
Anticancer Drugs · 2026 Jul · PMID 41601161 · Publisher ↗
Advanced hepatocellular carcinoma (HCC) with extensive metastases is associated with a poor prognosis, highlighting the need for individualized, multimodal treatment strategies. We present the case of a 54-year-old male...
Advanced hepatocellular carcinoma (HCC) with extensive metastases is associated with a poor prognosis, highlighting the need for individualized, multimodal treatment strategies. We present the case of a 54-year-old male with advanced HCC (cT3NxM1, Child-Pugh B) and spinal as well as bilateral pulmonary metastases who experienced disease progression after multiple lines of therapy. A dynamically adjusted, multidisciplinary regimen was implemented, incorporating transarterial chemoembolization (TACE), surgery, immunotherapy, and targeted therapy. The final regimen - combining nivolumab plus ipilimumab (O+Y) with TACE and lenvatinib - achieved a partial response in lung metastases, with a progression-free survival exceeding one year and overall survival of over 24 months. This case underscores the therapeutic potential of O+Y in later-line settings and demonstrates the clinical value of an integrated, personalized treatment paradigm for advanced HCC.
Human Epidermal Growth Factor Receptor-2 positive metastatic salivary duct carcinoma with remarkable response to targeted therapy: a case report and therapeutic implications.
Rodrigo Juan C, Climent Vicente C, Avilés Jurado FX … +3 more , Bartolomé Cerdà N, Lop Gros J, Mazariegos Rubi M
Anticancer Drugs · 2026 Jan · PMID 41601157 · Publisher ↗
Salivary duct carcinoma (SDC) is a rare and highly aggressive malignancy that frequently overexpresses Human Epidermal Growth Factor Receptor 2 (HER2). Despite the increasing recognition of HER2-targeted strategies, evid...
Salivary duct carcinoma (SDC) is a rare and highly aggressive malignancy that frequently overexpresses Human Epidermal Growth Factor Receptor 2 (HER2). Despite the increasing recognition of HER2-targeted strategies, evidence remains limited and largely derived from small trials and case series. We report the case of a middle-aged man with HER2-positive metastatic SDC who achieved near-complete pathologic and radiological response to trastuzumab and docetaxel, enabling surgical resection for locoregional control. This case highlights the role of anti-HER2 therapy as a first-line strategy in SDC and underscores the importance of individualized management plans integrating systemic treatment and locoregional measures.
Acquired FGFR2 mutation leads resistance to pemigatinib in a patient with FGFR2-driven Borrmann type IV gastric cancer.
Sun Q, Du S, Meng J … +1 more , Shi W
Anticancer Drugs · 2026 Jan · PMID 41563935 · Publisher ↗
Scirrhous gastric cancer (SGC), including the Borrmann type IV subtype, is characterized by a desmoplastic stroma, rapid progression, and a poor prognosis with limited effective treatment options. While fibroblast growth...
Scirrhous gastric cancer (SGC), including the Borrmann type IV subtype, is characterized by a desmoplastic stroma, rapid progression, and a poor prognosis with limited effective treatment options. While fibroblast growth factor receptor 2 (FGFR2) alterations are recognized therapeutic targets in some cancers, their clinical application in gastric cancer, particularly in SGC, remains underexplored. We present the case of a 47-year-old female with advanced, chemotherapy-refractory Borrmann type IV gastric cancer harboring FGFR2 rearrangement and amplification. Treatment with the selective FGFR1-3 inhibitor pemigatinib elicited a marked clinical and serological response; however, disease progression ensued after 3 months. Comprehensive genomic profiling revealed an acquired FGFR2 N549K mutation, a recognized on-target resistance mechanism. Subsequent administration of the irreversible FGFR1-4 inhibitor futibatinib was associated with a declining trend in tumor biomarkers, indicating preliminary antitumor activity against the resistant clone. This case underscores the clinical activity of FGFR inhibition in FGFR2-altered SGC and exemplifies the emergence of kinase domain mutations as a principal resistance pathway. It further suggests that irreversible FGFR inhibitors may represent a rational therapeutic strategy upon progression on prior FGFR-directed therapy, warranting further clinical investigation in this molecularly defined patient subset.
Dauricine induces ferroptosis in neuroblastoma by inhibiting methyltransferase-like 1-mediated N7-methylguanosine methylation of solute carrier family 3 member 2.
Tang L, Huang N, Li T … +1 more , Ren L
Anticancer Drugs · 2026 Jan · PMID 41546607 · Publisher ↗
Neuroblastoma is one of the most common extracranial solid tumors in children, characterized by high heterogeneity, aggressive biological behavior, and poor clinical prognosis. Ferroptosis, a form of programmed cell deat...
Neuroblastoma is one of the most common extracranial solid tumors in children, characterized by high heterogeneity, aggressive biological behavior, and poor clinical prognosis. Ferroptosis, a form of programmed cell death driven by iron accumulation and lipid peroxidation, has been reported to be closely associated with neuroblastoma progression. Dauricine (Dau), a bisbenzylisoquinoline alkaloid extracted from traditional Chinese medicine, has demonstrated antitumor activity, but its role in regulating ferroptosis in neuroblastoma remains unclear. Cell viability, apoptosis, invasion, stemness, and angiogenesis were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, terminal deoxynucleotidyl transferase dUTP nick end labeling, transwell, sphere formation, and tube formation assays, respectively. Ferroptosis-related indicators were detected using corresponding commercial kits. The methyltransferase-like 1 (METTL1)-mediated N7-methylguanosine (m7G) methylation of solute carrier family 3 member 2 (SLC3A2) was examined through methylated RNA immunoprecipitation. RNA immunoprecipitation and RNA pull-down assays were conducted to confirm the interaction between METTL1 and SLC3A2 mRNA. Real-time quantitative PCR and western blotting were utilized to assess mRNA and protein expression, respectively. Molecular docking was performed to evaluate the potential binding interaction between Dau and METTL1. A xenograft tumor model was used for in vivo validation. The results showed that Dau inhibited neuroblastoma cell progression and promoted ferroptosis, while overexpression of SLC3A2 countered these effects. METTL1 mediated the m7G methylation of SLC3A2. Overexpression of SLC3A2 reversed the inhibition of neuroblastoma cell progression and the promotion of ferroptosis caused by METTL1 knockdown. Dau suppressed METTL1 expression, thus inhibiting neuroblastoma cell progression and promoting ferroptosis. Additionally, Dau reduced tumor growth in vivo. Together, Dau enhanced ferroptosis and impeded neuroblastoma development by suppressing METTL1-mediated m7G methylation of SLC3A2, suggesting a novel therapeutic strategy for neuroblastoma.
The PITX2/CKMT1B axis promotes lung adenocarcinoma stemness via lipid accumulation.
Zhou L, Jin X, Shen Y … +2 more , Wang L, Jing J
Anticancer Drugs · 2026 Jan · PMID 41546562 · Publisher ↗
Dysregulated expression of mitochondrial creatine kinase 1B (CKMT1B), a member of the creatine kinase family, has been linked to tumor progression. However, its specific function in lung adenocarcinoma (LUAD) remains unc...
Dysregulated expression of mitochondrial creatine kinase 1B (CKMT1B), a member of the creatine kinase family, has been linked to tumor progression. However, its specific function in lung adenocarcinoma (LUAD) remains unclear. Bioinformatics analyses were performed to evaluate CKMT1B and its upstream transcription factor PITX2 in LUAD. CKMT1B and PITX2 expression levels were determined by quantitative PCR. The functional impact on cell stemness was subsequently evaluated using CCK-8, sphere formation assay, flow cytometry, and western blot. CKMT1B-mediated lipid accumulation was examined via BODIPY staining and measurements of triglyceride and glycerol concentration. The PITX2-CKMT1B interaction was validated through dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays, with the regulatory mechanism further substantiated by functional rescue experiments. CKMT1B was upregulated in LUAD and linked with poor prognosis. Its knockdown suppressed cell proliferation, sphere-forming capacity, and stemness-related protein expression (CD133, Bmi-1, SOX-2). Furthermore, CKMT1B overexpression facilitated lipid accumulation and stemness, effects that were reversible by the lipase inhibitor Orlistat. Mechanistically, PITX2 was identified as an upstream transcription factor of CKMT1B. PITX2 expression was positively correlated with CKMT1B, and high PITX2 expression predicted poor outcomes. In functional rescue experiments, PITX2 knockdown significantly reduced lipid accumulation and stemness, while these effects were partially restored by CKMT1B overexpression. PITX2 promotes lipid accumulation and enhances stemness in LUAD cells by transcriptionally activating CKMT1B, suggesting the PITX2/CKMT1B axis as a potential therapeutic target for LUAD treatment.
Isovanillin regulates gastric cancer cells apoptosis and metastasis by targeting ROS-mediated MAPK and PI3K signaling pathways.
Wen JJ, Jin XY, Luo YH … +5 more , Wu N, Tang YJ, Liu YZ, Liu Z, Jin CH
Anticancer Drugs · 2026 Jan · PMID 41546559 · Publisher ↗
Isovanillin, a natural coumarin compound, exhibits biological functions; however, its anti-gastric cancer process is not well understood. This research examined the pathway underlying isovanillin's effects on gastric can...
Isovanillin, a natural coumarin compound, exhibits biological functions; however, its anti-gastric cancer process is not well understood. This research examined the pathway underlying isovanillin's effects on gastric cancer cells. Cell viability assays demonstrated that isovanillin effectively reduced the viability of various gastric cancer cell lines. Network pharmacological analysis identified 41 key targets implicated in isovanillin's anti-gastric cancer activity, highlighting the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), mitogen-activated protein kinase (MAPK), and reactive oxygen species (ROS) pathways as critical components. Apoptosis assays revealed that isovanillin promoted apoptosis by upregulating the manifestation of p-p38 and p-JNK and suppressing p-ERK and p-STAT3. Cellular cycle examination revealed that isovanillin triggered G2/M stage block via the suppression of p-PI3K, p-AKT, cell cycle regulators 1/2 (CDK1/2), and cyclin B1, and the increase of cell cycle inhibitor 1A (p21) and cell cycle inhibitor 1B (p27). Cell metastasis assays showed that isovanillin suppressed the migration of MKN-45 cells through diminishing the concentrations of p-PI3K, p-AKT, N-cadherin, matrix metalloproteinase-2, as well as matrix metalloproteinase-9, while increasing E-cadherin expression. Furthermore, isovanillin exerted its anti-gastric cancer effects by promoting ROS accumulation, thereby modulating associated signaling pathways. The ROS scavenger N-acetyl-l-cysteine reversed isovanillin-induced protein expression changes. In conclusion, isovanillin induces apoptosis, G2/M phase arrest, and inhibits MKN-45 cell migration by mediating ROS to regulate the MAPK and PI3K signaling pathways.
Evaluation of the protective effect of chamomile oral solution on the incidence of neurotoxicity caused by paclitaxel in breast cancer patients.
Nikkhah N, Karbasforooshan H, Shahid Sales S … +4 more , Hosseini S, Akhlaghi S, Amiri Tehranizadeh Z, Elyasi S
Anticancer Drugs · 2026 Jan · PMID 41538720 · Publisher ↗
Neurotoxicity is one of the major complications in cancer patients following paclitaxel-containing regimens. Matricaria chamomilla L., isolated from the German chamomile, has anti-inflammatory and antioxidant features. I...
Neurotoxicity is one of the major complications in cancer patients following paclitaxel-containing regimens. Matricaria chamomilla L., isolated from the German chamomile, has anti-inflammatory and antioxidant features. In this study we evaluated the preventive impact of a chamomile oral formulation against paclitaxel-induced neurotoxicity in cancer patients. In this triple-blind clinical trial, cancer patients on paclitaxel were randomly allocated to chamomile oral solution (n = 40), or the placebo (n = 40) 5 ml three times a day for four courses of chemotherapy starting one day before the paclitaxel injection. At the end of each chemotherapy course, patients in both groups were evaluated and graded according to CTCAE (Common Terminology Criteria for Adverse Events). Also, anxiety and sleep disorder were evaluated at the beginning and end of the study based on Generalized Anxiety Disorder-7 and Pittsburgh Sleep Quality Index criteria, respectively. At the end of the four cycles of chemotherapy, there was no significant difference between the two groups in terms of the neuropathy CTCAE score. In terms of the various components of the sleep questionnaire, only the individual's overall description of sleep quality at the end of the study was significantly better in the treatment group (P = 0.026). Sleep quality was also significantly better (P = 0.027), and the chance of good sleep quality in the intervention group was 4.48 times higher. Regarding the anxiety score, despite a significant decrease in both groups, the difference between the two groups at the end of the fourth course was not significant. Neither group experienced any adverse effects. Although chamomile oral solution did not significantly lessen neuropathy, findings propose that it may significantly ameliorate sleep quality in patients receiving chemotherapy as a low-cost, low-risk treatment. It also has no significant impact on reducing the level of anxiety in cancer patients.
Efficacy and safety of fulvestrant combined with abemaciclib in patients with hormone receptor-positive advanced breast cancer.
Su L, Du Y, Yao J … +5 more , Wang M, Zhang G, Luo L, Yao C, Zhao J
Anticancer Drugs · 2026 Jan · PMID 41503870 · Publisher ↗
This study evaluated the efficacy and safety of fulvestrant combined with abemaciclib in patients with hormone receptor-positive advanced breast cancer and compared the outcomes with those reported in the MONARCH 2 trial...
This study evaluated the efficacy and safety of fulvestrant combined with abemaciclib in patients with hormone receptor-positive advanced breast cancer and compared the outcomes with those reported in the MONARCH 2 trial. Forty-six patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer received fulvestrant 500 mg administered intramuscularly (days 1, 15, and 28, then every 28 days) combined with abemaciclib 150 mg taken orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. All 46 patients were evaluable for efficacy. No complete response was observed; 21 patients (45.7%) achieved partial response, 8 (17.4%) had stable disease, and 17 (37.0%) experienced progressive disease (PD). The ORR was 45.7%, and the DCR was 63.0%. Median PFS was 19.1 months (95% confidence interval: 16.0-NR). Compared with the MONARCH 2 trial, ORR was slightly higher (45.7% vs. 35.2%), whereas the DCR was lower (63.0% vs. 83.0%), accompanied by a markedly higher PD rate (37.0% vs. 9.0%, P < 0.001). The most frequently reported adverse events were leukopenia (30.4%), nausea/vomiting (47.8%), and fatigue (32.6%), consistent with findings from MONARCH 2, with no new safety signals identified. Fulvestrant combined with abemaciclib demonstrated antineoplastic activity and a manageable safety profile in patients with hormone receptor-positive advanced breast cancer. Relative to the MONARCH 2 trial, this real-world cohort exhibited a higher ORR but a lower DCR, potentially reflecting differences in prior treatments and baseline characteristics. Additional large-scale, multicenter studies are warranted to validate these findings.
Fibroblast growth factor receptor 2 mutation-guided targeted therapy with lenvatinib in sebaceous carcinoma of the external auditory canal: a case report and literature review.
Zhao R, Han Q, Wen J … +5 more , Zhang X, Qiu W, Wu S, Gao L, Zhao X
Anticancer Drugs · 2026 Jul · PMID 41503867 · Publisher ↗
This is the first global report of a successful case of lenvatinib treatment for a rare sebaceous carcinoma originating in the external auditory canal. The patient experienced local recurrence and pulmonary metastasis de...
This is the first global report of a successful case of lenvatinib treatment for a rare sebaceous carcinoma originating in the external auditory canal. The patient experienced local recurrence and pulmonary metastasis despite undergoing surgery and radiotherapy. Initial chemotherapy combined with immune checkpoint inhibitors achieved short-term stability, but the disease eventually progressed. Genetic testing revealed an Fibroblast growth factor receptor 2 (FGFR2) mutation, leading to a switch to targeted therapy with lenvatinib combined with capecitabine, demonstrating the value of targeted therapy in the management of rare, refractory sebaceous carcinoma.
Comparative study of the efficacy and safety of PSOX and SOX plus sintilimab regimens as first-line treatments for advanced gastric cancer.
Zhang T, Yang W, Zhang C … +2 more , Wang K, Li H
Anticancer Drugs · 2026 Jul · PMID 41503711 · Full text
Advanced gastric cancer (AGC) remains associated with poor survival despite advances in multimodal treatment. Recent trials suggest that adding programmed death-1 inhibitors to chemotherapy may improve outcomes in HER2-n...
Advanced gastric cancer (AGC) remains associated with poor survival despite advances in multimodal treatment. Recent trials suggest that adding programmed death-1 inhibitors to chemotherapy may improve outcomes in HER2-negative AGC, but real-world evidence-particularly in surgical settings-remains limited. This retrospective study evaluated the efficacy and safety of SOX plus sintilimab compared with P-SOX in patients with AGC undergoing perioperative chemotherapy followed by standard D2 gastrectomy. A total of 242 patients were included, of whom 161 received P-SOX and 81 received SOX plus sintilimab. Short-term response, long-term survival outcomes, and treatment-related adverse events were compared between groups. Prognostic factors for progression-free survival (PFS) were further analyzed in patients treated with SOX plus sintilimab. The SOX plus sintilimab regimen achieved superior short-term efficacy, with higher objective response rates by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (70.4% vs. 47.2%) and higher tumor regression grades (91.4% vs. 72.7%) compared with P-SOX (both P < 0.001). Median overall survival was significantly longer in the SOX plus sintilimab group (32.0 vs. 29.0 months; HR = 0.617, P = 0.006), while PFS showed a borderline improvement. Treatment-related adverse events were mostly grade 1-2, with comparable rates of severe toxicities between groups; immune-related events were infrequent. Poor perioperative treatment response, larger tumor size, poor differentiation, and advanced stage were independently associated with worse PFS. In conclusion, SOX plus sintilimab offers improved efficacy with acceptable safety compared with P-SOX, providing supportive real-world evidence for its use in AGC.
Hematopoietic progenitor kinase 1 inhibitor BGB-15025 induces apoptosis in acute myeloid leukemia cells through the cell cycle pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway signaling axis.
Yang S, Li F, Zhuang H … +7 more , Chen D, Jiang X, Zhou Y, Pei R, Li S, Ye P, Lu Y
Anticancer Drugs · 2026 Jun · PMID 41503684 · Full text
Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy originating from the malignant clonal proliferation of hematopoietic stem/progenitor cells and is associated with a poor prognosis. Hematopoie...
Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy originating from the malignant clonal proliferation of hematopoietic stem/progenitor cells and is associated with a poor prognosis. Hematopoietic progenitor kinase 1 (HPK1, MAP4K1), a member of the MAP4K family, plays a critical role in immunomodulation and oncogenesis. Previous studies have highlighted its pro-oncogenic function in AML, suggesting its potential as both a prognostic marker and therapeutic target. This study aimed to investigate the anti-AML effects of the novel HPK1 inhibitor BGB-15025. We utilized preclinical models, including AML cell lines, primary patient-derived cells, and MV4-11 xenograft mice. Mechanistic investigations were conducted using RNA sequencing and Western blot analysis. BGB-15025 exerted potent cytotoxicity against AML cells and primary progenitors, inducing apoptosis and G0/G1 cell cycle arrest via downregulation of cyclin D1-cyclin-dependent kinase 4 and upregulation of P21. The inhibitor suppressed mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling through reduced phosphorylation of P38 and ERK. In-vivo studies demonstrated a reduced leukemia burden in xenograft models. This study is the first to elucidate that BGB-15025 triggers AML apoptosis through cell cycle blockade and MAPK pathway inhibition, thereby proposing a novel precision therapeutic strategy with significant clinical translational value.
Aldehyde dehydrogenase 9A1 promotes cisplatin resistance in laryngeal squamous cell carcinoma by enhancing PTEN-induced kinase 1-Parkin-mediated mitophagy.
Gui J, Wu B, Fan Y … +9 more , Liu X, Liu Y, Wang H, An J, Wang H, Wu R, Li L, Ge J, Xiao H
Anticancer Drugs · 2026 Jul · PMID 41437516 · Publisher ↗
Cisplatin resistance remains a major challenge in laryngeal squamous cell carcinoma (LSCC) treatment. Aldehyde dehydrogenase 9A1 (ALDH9A1), a mitochondrial matrix protein, is dysregulated in various cancers, but its role...
Cisplatin resistance remains a major challenge in laryngeal squamous cell carcinoma (LSCC) treatment. Aldehyde dehydrogenase 9A1 (ALDH9A1), a mitochondrial matrix protein, is dysregulated in various cancers, but its role in LSCC is unclear. This study demonstrates that ALDH9A1 is significantly downregulated in LSCC tissues, and low ALDH9A1 expression correlates with poor patient prognosis. Functionally, ALDH9A1 overexpression inhibits LSCC cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, ALDH9A1 interacts with and stabilizes PTEN-induced kinase 1 (PINK1), leading to activation of PINK1-Parkin-mediated mitophagy. Under cisplatin treatment, ALDH9A1 is upregulated and induces protective mitophagy, contributing to cisplatin resistance. Inhibition of mitophagy with chloroquine sensitizes LSCC cells to cisplatin. These findings identify ALDH9A1 as a key regulator of mitophagy and cisplatin resistance in LSCC, suggesting that targeting the ALDH9A1/PINK1 axis could provide a novel therapeutic strategy for overcoming cisplatin resistance.
The evolving landscape of KRAS-targeted therapy: mechanisms of resistance and emerging strategies.
Pilco-Janeta DF, De la Cruz-Puebla M
Anticancer Drugs · 2026 Mar · PMID 41437507 · Publisher ↗
Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are among the most common oncogenic drivers in human cancer and are associated with poor prognosis, limited therapeutic options, and frequent resistance to stan...
Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are among the most common oncogenic drivers in human cancer and are associated with poor prognosis, limited therapeutic options, and frequent resistance to standard treatments. The approval of the first direct KRAS G12C inhibitors demonstrated that mutant KRAS can be targeted clinically, but their efficacy is restricted to a narrow allelic subset and is limited by adaptive resistance. This review summarizes recent advances in KRAS-targeted drug development beyond G12C and outlines emerging strategies designed to improve therapeutic outcomes. A comprehensive literature review was conducted using preclinical and clinical data from studies investigating KRAS inhibitors, rat sarcoma (RAS) pathway modulators, and rational drug combinations. Particular attention was given to allele-specific agents, pan-RAS inhibitors, feedback signaling mechanisms, and resistance biology. Next-generation KRAS inhibitors targeting non-G12C alleles, including KRAS G12D selective agents, have demonstrated potent preclinical activity but remain susceptible to feedback mitogen-activated protein kinase (MAPK) reactivation. Pan-RAS inhibitors that bind the active RAS-GTP state show activity across multiple alleles and tumor types, although toxicity and therapeutic window remain key concerns. Indirect strategies targeting SHP2, SOS1, and downstream MAPK components enhance pathway suppression and delay resistance, especially in combination with direct KRAS inhibitors. Resistance mechanisms encompass secondary KRAS mutations, bypass signaling through alternative RAS isoforms, and activation of parallel pathways. Comutations such as STK11 or KEAP1 further influence therapeutic response and immune contexture. KRAS-directed therapy is rapidly expanding beyond G12C, with allele-specific inhibitors, pan-RAS approaches, and rational combinations offering new opportunities for broader clinical benefit. Ongoing challenges include toxicity management, resistance evolution, and the development of predictive biomarkers to guide therapy selection.
Clinical importance of the interactions between the TGF-β1/SMAD and NF-κB pathways in colorectal cancer and the study of the synergistic regulatory mechanism of the STAT3-mediated pathway.
Chao H, Liu H, Shen W
Anticancer Drugs · 2026 Mar · PMID 41437372 · Publisher ↗
This study aimed to explore the clinical significance and potential mechanisms of the transforming growth factor- β1 (TGF-β1)/small mother against decapentaplegic (SMAD) and nuclear factor kappa B (NF-κB) pathways in col...
This study aimed to explore the clinical significance and potential mechanisms of the transforming growth factor- β1 (TGF-β1)/small mother against decapentaplegic (SMAD) and nuclear factor kappa B (NF-κB) pathways in colorectal cancer (CRC). Transcriptomic and clinical data of CRC patients were retrieved from TCGA and GEO databases, analyzed via TCGAbiolinks, GEPIA 2, KEGG, and GO. A total of 275 colon cancer and 92 rectal cancer samples were included. Results showed TβR2 and SMAD2 expression was significantly associated with CRC pathological stage ( P < 0.05), while low TGF-β1, TβR1, and TβR2 expression correlated with longer disease-free survival (DFS, P < 0.05). Pathway component correlations differed between normal and cancerous tissues; high co-expression of NF-κB1 and SMAD2 linked to longer DFS in rectal cancer ( P < 0.05). Signal transducer and activator of transcription 3 (STAT3) strongly correlated with NF-κB1, SMAD2/4 (R = 0.7, 0.63, 0.65; P < 0.001), and combinations of NF-κB1 with SMAD2/SMAD4 showed strong correlations with STAT3 (R = 0.73; P < 0.001). NF-κB1 combined with SMAD2 has prognostic value for rectal cancer, and STAT3 may be a common upstream transcription factor regulating both pathways.
Interferon regulatory factor 4 drives M2 macrophage polarization in lung adenocarcinoma via the absent in melanoma 2-mediated phosphoinositide 3-kinase/protein kinase B signaling pathway.
Zou X, Ji Q, Wen Z … +3 more , Lei L, Chen X, Hu W
Anticancer Drugs · 2026 Jun · PMID 41437307 · Publisher ↗
Tumor-associated macrophages, predominant immunosuppressive components within the tumor microenvironment, critically regulate lung adenocarcinoma (LUAD) progression; however, their molecular regulatory mechanisms remain...
Tumor-associated macrophages, predominant immunosuppressive components within the tumor microenvironment, critically regulate lung adenocarcinoma (LUAD) progression; however, their molecular regulatory mechanisms remain incompletely characterized. The Cancer Genome Atlas database analysis revealed absent in melanoma 2 (AIM2) expression in LUAD. The correlation between AIM2 expression and M2 macrophage infiltration levels was further evaluated. Putative transcriptional regulators upstream of AIM2 were predicted through bioinformatics screening, with JASPAR employed to identify potential binding sites between candidate factors and the AIM2 promoter. These predictions were experimentally validated using dual-luciferase reporter assays. Furthermore, we established a LUAD cell-macrophage coculture system. We performed flow cytometric analysis of macrophage surface CD206 expression, quantitative PCR quantification of mRNA levels, ELISA quantification of cytokine secretion profiles, and Western blot detection of proteins. Bioinformatics analysis revealed that AIM2 was highly expressed in LUAD tumor tissues and positively correlated with the marker genes of M2 macrophages. Overexpression of AIM2 in LUAD cells promoted the expression of CD206 on the macrophage surface, upregulated the mRNA expression levels of M2 macrophage marker genes such as CD163 , ARG1 , and MRC1 , and enhanced the secretion of transforming growth factor-beta and interleukin-10 . These results indicated an increased level of macrophage polarization towards the M2 phenotype, and inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway reversed the above phenomenon. Furthermore, the interferon regulatory factor 4 (IRF4) promoted the transcription of AIM2. IRF4 knockdown in LUAD cells suppressed M2 macrophage polarization, but simultaneous overexpression of AIM2 restored it to baseline levels. IRF4 drives M2 macrophage polarization in LUAD via the AIM2-mediated PI3K/AKT signaling pathway.
Survival advantage of bevacizumab rechallenge in recurrent ovarian cancer regardless of platinum sensitivity.
Ozberk U, Esen SA, Sekmek S … +5 more , Seven I, Bal O, Algin E, Yucel S, Uncu D
Anticancer Drugs · 2026 Jul · PMID 41430637 · Publisher ↗
Bevacizumab has demonstrated significant efficacy in both first-line and recurrent settings of epithelial ovarian cancer; however, evidence regarding the benefit of bevacizumab retreatment after prior exposure in real-wo...
Bevacizumab has demonstrated significant efficacy in both first-line and recurrent settings of epithelial ovarian cancer; however, evidence regarding the benefit of bevacizumab retreatment after prior exposure in real-world populations remains limited. This study aimed to evaluate the efficacy of bevacizumab retreatment compared with nonbevacizumab regimens in recurrent metastatic ovarian carcinoma, irrespective of platinum sensitivity status. This retrospective single-center study included 133 patients with recurrent epithelial ovarian cancer who had previously received bevacizumab-containing first-line therapy between January 2015 and May 2025. Patients were grouped according to second-line treatment: bevacizumab-containing chemotherapy ( n = 51) or chemotherapy alone ( n = 82). Patients undergoing secondary cytoreductive surgery were excluded. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression models. Median PFS-2 after second-line treatment was significantly longer in the bevacizumab group compared with the nonbevacizumab group (9.7 vs. 3.0 months; P < 0.001). This benefit was consistent across both platinum-sensitive and platinum-resistant subgroups. Multivariate analysis confirmed that omission of bevacizumab independently predicted worse PFS-2 (hazard ratio = 3.33, 95% CI: 2.17-5.11, P < 0.001). Although OS-2 was numerically longer in the bevacizumab group (14.1 vs. 8.2 months), the difference was not statistically significant ( P = 0.091). Bevacizumab retreatment following prior first-line use was associated with improved PFS regardless of platinum sensitivity, suggesting a potential survival advantage in recurrent ovarian cancer. Prospective, randomized studies including both platinum-sensitive and platinum-resistant patients with larger sample sizes are warranted to confirm these findings and determine the optimal use of bevacizumab beyond first-line therapy.
Apatinib triggers ferroptosis in gastric cancer via HDAC1/HIF1α/CA9 signaling axis.
Meng L, Cao L, Lu Y … +2 more , Yang L, Zhu W
Anticancer Drugs · 2026 Mar · PMID 41372108 · Publisher ↗
Gastric cancer (GC) poses significant therapeutic challenges due to frequent late-stage diagnosis and limited treatment efficacy. Although Apatinib demonstrates clinical benefits in GC, acquired resistance remains proble...
Gastric cancer (GC) poses significant therapeutic challenges due to frequent late-stage diagnosis and limited treatment efficacy. Although Apatinib demonstrates clinical benefits in GC, acquired resistance remains problematic. Ferroptosis induction represents a promising strategy to overcome such resistance. Integrated computational target prediction (SwissTargetPrediction) and ferroptosis suppressor gene screening (FerrDb) identified carbonic anhydrase IX (CA9) as Apatinib's putative target. Functional validation employed EdU, Transwell, sphere-formation, and flow cytometry assays. Ferroptosis markers [Fe²⁺, reactive oxygen species (ROS), ACSL4, and GPX4] were quantified via specific kits and western blotting. Histone deacetylase 1 (HDAC1)/hypoxia inducible factor 1α (HIF1α)/CA9 axis regulation was assessed through overexpression, siRNA knockdown, and immunoprecipitation. Apatinib significantly suppressed GC cell proliferation, migration, and stemness while promoting apoptosis. It induced ferroptosis via Fe²⁺/ROS accumulation and abnormal ACSL4/GPX4 expression. Mechanistically, Apatinib downregulated HDAC1, triggering HIF1α ubiquitination and subsequent CA9 suppression. HDAC1 overexpression reversed Apatinib-induced ferroptosis and antitumor effects, whereas HIF1α knockdown abrogated this rescue. This study elucidates a novel HDAC1/HIF1α/CA9 axis through which Apatinib induces ferroptosis. Targeting this pathway offers translational potential for overcoming Apatinib resistance in GC therapy.
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