Anti-cancer Drugs[JOURNAL]
Sun
200 papers
Eugenol as a game-changer: overcoming osimertinib resistance in non-small cell lung cancer by inhibiting glycolysis via the tripartite motif containing 59/extracellular signal-regulated kinase pathway.
Zhao K, Wang W, Sun Y … +1 more , Li K
Anticancer Drugs · 2026 Jun · PMID 41372105 · Full text
Eugenol plays a significant role in various cancers and can influence the sensitivity of cancer cells to chemotherapy. This study aimed to investigate the mechanism by which eugenol regulates glycolysis through the tripa...
Eugenol plays a significant role in various cancers and can influence the sensitivity of cancer cells to chemotherapy. This study aimed to investigate the mechanism by which eugenol regulates glycolysis through the tripartite motif containing 59 (TRIM59)/extracellular signal-regulated kinase (ERK) pathway in osimertinib-resistant non-small cell lung cancer (NSCLC). Drug-resistant lung cancer cell lines were established using osimertinib and treated with eugenol at different concentrations for 24 h. After treatment with eugenol, siTRIM59, TRIM59 overexpression, and the ERK inhibitor, either alone or in combination, the cell counting kit-8 was used to assess cell viability in drug-resistant cell lines. Flow cytometry, colony formation assay, and transwell assays were employed to evaluate the effects of eugenol on cell apoptosis, clonogenic ability, migration, and invasion, respectively. Relevant kits were used to measure the glycolytic activity of the cells. Eugenol inhibited the proliferation, invasion, and migration of drug-resistant cells, promoted apoptosis, and reduced glucose consumption, lactate release, and glycolytic activity in drug-resistant cells. TRIM59 expression was higher in drug-resistant cancer cells, while eugenol treatment inhibited the expression of TRIM59 and ERK phosphorylation. Silencing of TRIM59 enhanced the effect of eugenol on drug-resistant cell lines. Overexpression of TRIM59 reversed the effects of eugenol on drug-resistant cell lines, whereas ERK inhibition reversed the effects of TRIM59 and enhanced the therapeutic effects of eugenol on cancer cells. Moreover, eugenol inhibited the tumor growth, TRIM59 expression, and ERK phosphorylation in osimertinib-treated mice. Eugenol can effectively overcome osimertinib resistance in NSCLC by regulating glycolysis through the TRIM59/ERK signaling pathway. Eugenol could serve as a promising adjunctive therapy to improve chemotherapy efficacy and overcome drug resistance in NSCLC.
Treatment of HRD-positive elderly ovarian cancer patient: a case report.
Jiang Y, Yi Q, Wang Y … +2 more , Li C, Liu H
Anticancer Drugs · 2026 Jun · PMID 41314654 · Full text
The standard treatment for advanced ovarian cancer follows a comprehensive 'surgery-chemotherapy-maintenance therapy' mode, typically involving initial cytoreductive surgery aiming for R0 resection, six cycles of platinu...
The standard treatment for advanced ovarian cancer follows a comprehensive 'surgery-chemotherapy-maintenance therapy' mode, typically involving initial cytoreductive surgery aiming for R0 resection, six cycles of platinum-based chemotherapy, followed by maintenance therapy for those who have responded well to the treatment. However, frailty and high incidence of comorbidities in elderly patients often compromise surgical outcomes, necessitate chemotherapy dose reductions, and limit maintenance therapy continuation, resulting in a poor prognosis. Poly (Adenosine diphosphate (ADP)-ribose) polymerase inhibitors (PARPi) have revolutionized the management strategy of homologous recombination deficiency (HRD)-positive patients as a groundbreaking advancement in first-line maintenance therapy. Fluzoparib, the domestically developed PARPi in China, has demonstrated significant efficacy in BRCA-mutated ovarian cancer. In the field of supportive care, megestrol acetate (MA) is recommended as the first-line preferred therapeutic agent for cancer-related anorexia by major guidelines, though its role in first-line ovarian cancer therapy remains unexplored, and evidence for its combination with PARPi is lacking. This article reported a case of an 89-year-old female patient with high-grade serous ovarian carcinoma. Due to intolerance to surgery and chemotherapy, an innovative first-line primary treatment regimen combining fluzoparib with MA was initiated based on BRCA2 mutation and HRD-positive status. Imaging assessments revealed significant tumor reduction without disease progression or grade ≥3 adverse events observed throughout follow-up. This case highlights the potential of combining PARPi and hormone therapy as a 'chemotherapy-free' precision treatment model for elderly and HRD-positive ovarian cancer patients, offering a promising strategy to balance efficacy and tolerability in a population traditionally underserved by conventional regimens.
EP4 influences bortezomib resistance in multiple myeloma by modulating endoplasmic reticulum stress via the phosphatidylinositol 3-kinase/protein kinase B pathway.
Shi T, Chen Y, Liu Z … +1 more , Liu A
Anticancer Drugs · 2026 Apr · PMID 41243487 · Full text
Multiple myeloma, a hematologic malignancy characterized by the uncontrolled proliferation of plasma cells, presents a significant therapeutic challenge, particularly due to the development of resistance to bortezomib, a...
Multiple myeloma, a hematologic malignancy characterized by the uncontrolled proliferation of plasma cells, presents a significant therapeutic challenge, particularly due to the development of resistance to bortezomib, a cornerstone in its treatment. The prostaglandin E receptor 4 (PTGER4 or EP4), a component of the prostaglandin E2 signaling pathway, has emerged as a potential modulator of drug resistance. However, its precise mechanistic role in multiple myeloma remains inadequately understood. This study aims to elucidate the role of EP4 in bortezomib resistance, specifically focusing on its interaction with the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. We employed a comprehensive approach that integrates bioinformatics analysis of multiple myeloma-related genes from public databases with advanced molecular biology techniques. Our investigation examined EP4 expression in both bortezomib-resistant and bortezomib-sensitive multiple myeloma cell lines. The impacts of EP4 overexpression on various cellular processes, including proliferation, apoptosis, endoplasmic reticulum (ER) stress, and bortezomib sensitivity, were examined. Both in vitro and in vivo experiments were conducted to delineate the role of EP4 in modulating the PI3K/AKT pathway and its downstream effects on drug resistance. Our findings revealed a significant decrease in EP4 expression in multiple myeloma tissues, with important implications for patient survival and prognosis. Overexpression of EP4 in bortezomib-resistant cell lines enhanced their sensitivity to the drug, inhibited cell growth, and induced apoptosis. These effects were accompanied by decreased phosphorylation of PI3K and AKT, along with increased expression of glucose-regulated protein 78 000, an indicator of ER stress. Notably, these effects were partially reversed when combined with treatment using an AKT agonist. EP4 plays a significant role in modulating bortezomib resistance in multiple myeloma through its effects on the PI3K/AKT pathway and ER stress. These findings underscore the therapeutic potential of targeting EP4 to enhance bortezomib efficacy and improve clinical outcomes for patients with multiple myeloma.
A new anilinoquinazoline derivative, F307 induces autophagy and differential apoptosis in wild-type and mutated-epidermal growth factor receptor non-small cell lung cancer cell lines.
Keflee RD, Leong KH, Abdulwahab MK … +2 more , Ariffin A, Kong KW
Anticancer Drugs · 2026 Jan · PMID 41191814 · Publisher ↗
Non-small-cell lung cancer (NSCLC) often develops epidermal growth factor receptor (EGFR) mutations that respond poorly to chemotherapy with complicated resistance mechanisms, limiting the long-term treatment success. Th...
Non-small-cell lung cancer (NSCLC) often develops epidermal growth factor receptor (EGFR) mutations that respond poorly to chemotherapy with complicated resistance mechanisms, limiting the long-term treatment success. This study is to determine the functional impact and molecular mechanisms of the F307 compound in NSCLC cell lines harboring either wild-type or mutant EGFR. Cell proliferation in NSCLC cell lines was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays in a time- and dose-dependent manner. Apoptosis and cell cycle distribution were analyzed via flow cytometry, supported by caspase activity assays and morphological evaluations. Western blotting was used to quantify key proteins involved in cell cycle regulation, autophagy, apoptosis, and EGFR signaling. F307, a new anilinoquinazoline derivative, demonstrated potent antiproliferative effects in a time- and dose-dependent manner. It induced autophagic activity in both A549 and H1975 cells. In A549 cells, F307 promoted caspase-dependent apoptosis via the intrinsic mitochondrial pathway, whereas in H1975 cells via a caspase-independent mechanism, characterized by poly (ADP-ribose) polymerase cleavage. This is accompanied by increased p53 expression in A549 and decreased mutant p53 levels in H1975 cells. Cell cycle analysis revealed G2/M phase arrest in both cell lines, with increased p21 expression. F307 effectively inhibited EGFR phosphorylation and downstream phosphoinositide 3-kinase signaling, leading to reduced extracellular signal-regulated kinase and protein kinase B phosphorylation in A549 cells and elevated levels in H1975 cells. This study highlights EGFR as a key target in NSCLC and provides additional insights of F307's antitumor activity, but further improvement to the compound and biological studies are needed to uncover its potential for further therapeutic development.
Precision design of an HLA-I-targeted multiepitope vaccine against human papillomavirus 16 oncoproteins E6/E7: integrated immunoinformatic and immunogenicity profiling.
Dai J, Yang R, Cun Y … +8 more , Zhang X, Li J, Shi L, Zhou L, Tao Y, Shi L, Yao Y, Liu S
Anticancer Drugs · 2026 Jan · PMID 41191800 · Publisher ↗
Viral oncogenes E6 and E7 are ideal targets for therapeutic vaccines against human papillomavirus (HPV)-associated cervical cancer (CC). T cell-mediated immunity plays a crucial role in the clearance of HPV infection and...
Viral oncogenes E6 and E7 are ideal targets for therapeutic vaccines against human papillomavirus (HPV)-associated cervical cancer (CC). T cell-mediated immunity plays a crucial role in the clearance of HPV infection and regression of intraepithelial neoplasia. Current strategies for therapeutic vaccine development predominantly depend on immunoinformatic predictions of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocyte (CTL) epitopes. Three T-cell epitope prediction programs were used to identify HPV16 E6 and E7 epitopes restricted to HLA-A*02:01. Subsequently, in silico evaluations were performed using five bioinformatic databases and computational servers. The binding affinities of these peptides to HLA-A2 molecules were experimentally validated using a T2 cell-binding assay. The effectiveness of the vaccine developed by combining peptides and CpG-containing oligonucleotide (CpG-ODN) was validated by inducing the generation of CTLs ex vivo, and its immunogenicity was verified in HLA-A*02:01/H-2D d (AAD) transgenic mice. Eight HLA-A*02:01-restricted candidate peptides were preliminarily identified, and all candidate peptides demonstrated binding capabilities to HLA-A2 molecules. Using the integrated approach, four high-affinity peptides were successfully identified. Notably, these peptides also exhibited the potential to induce dendritic cell maturation, enhance the activation and proliferation of CD8 + T cells, and elicit potent antigen-specific CTL responses against tumor cells. These findings support the potential application of the selected peptides in CTL-based immunotherapy for HPV-driven malignancies. Furthermore, the described peptide-screening platform proved to be an effective strategy for the rational design of candidate antigens for HPV therapeutic vaccines.
Ubiquitylation-oxaliplatin-related prognosis signature reveals the landscapes of immune responses, cell communication, and therapeutic sensitivity for colorectal cancer.
Zhang G, Chen X
Anticancer Drugs · 2026 Jan · PMID 41191789 · Full text
Ubiquitylation plays a crucial role in posttranslational modification, and its dysregulation is linked to chemosensitivity. However, its role in oxaliplatin (OXA) resistance in colorectal cancer (CRC) remains unclear. Tr...
Ubiquitylation plays a crucial role in posttranslational modification, and its dysregulation is linked to chemosensitivity. However, its role in oxaliplatin (OXA) resistance in colorectal cancer (CRC) remains unclear. Transcriptomic data from the cancer genome atlas (TCGA) and Gene Expression Omnibus were used to develop a ubiquitylation-OXA resistance-related risk score (URGScore), integrating immunological, mutational, and clinical features. Single-cell RNA sequencing (scRNA-seq) identified OXA-resistant cell populations, and Genomics of Drug Sensitivity in Cancer predicted drug sensitivity. GSVA analyzed enriched pathways. Ubiquitin-specific protease 7 (USP7) expression and function were validated in CRC. A 10-gene OXA resistance signature effectively classified CRC patients into OXA-sensitive or -resistant groups. Low-URGScore patients showed greater benefit from immunotherapy. scRNA-seq highlighted the MK signaling pathway, particularly in dendritic cells and progenitors, with NCL as a key MK receptor directly interacting with USP7. Potential drugs for high-risk patients were identified. Functionally, USP7 promoted CRC proliferation, invasion, and OXA resistance in vitro. We generated an ubiquitylation-OXA-resistant CRC risk model that was employed to provide potential therapeutic targets and strategies for treating CRC patients exhibiting OXA-resistance.
Activation of the caspase-1/gasdermin D pathway via α-linolenic acid-mediated GPR120 signaling induces pyroptosis and suppresses ovarian cancer tumor growth.
Sun S, Qian L
Anticancer Drugs · 2026 Mar · PMID 41191783 · Full text
To investigate the role and underlying mechanism of α-linolenic acid (ALA) in ovarian cancer (OC), particularly its relationship with pyroptosis and the GPR120/caspase-1/Gasdermin D (GSDMD) pathway. Human OC cell lines (...
To investigate the role and underlying mechanism of α-linolenic acid (ALA) in ovarian cancer (OC), particularly its relationship with pyroptosis and the GPR120/caspase-1/Gasdermin D (GSDMD) pathway. Human OC cell lines (SKOV3, A2780), THP-1 monocytes, and SKOV3 subcutaneous xenograft models in nude mice were employed. Key assays included cell counting kit-8 (CCK-8) for cell viability, lactate dehydrogenase release for membrane damage detection, ELISA for Interleukin-1β (IL-1β) and IL-18 measurement, Western blot and quantitative polymerase chain reaction (qPCR) for analyzing pyroptosis-related molecules, molecular docking for ALA-GPR120 binding, and flow cytometry. Mice were administered ALA at a dose of 50 mg/kg by intraperitoneal injection, twice weekly for 4 weeks, or saline. ALA induced pyroptosis in OC cells both in vitro and in vivo, accompanied by increased membrane damage, elevated levels of IL-1β and IL-18, and activation of pyroptosis-related molecules. It targeted and inhibited GPR120 to activate the caspase-1/GSDMD pathway, with GSDMD identified as a critical effector. ALA also promoted M1 macrophage polarization and inhibited OC cell activity. In vivo, ALA reduced tumor size, upregulated pyroptosis markers, downregulated GPR120, and caused no significant toxicity. ALA induces OC cell pyroptosis and modulates the tumor microenvironment via the GPR120/caspase-1/GSDMD pathway, safely inhibiting OC growth. This reveals a novel mechanism, supporting ALA as a potential therapeutic candidate for OC, though further research into downstream regulation is required.
A novel anticancer natural product SP09 selectively targets KRAS-mutant NSCLC through LKB1/AMPK/mTOR modulation: implications for novel therapeutic development.
Yue P, Hon C, Zhao X … +3 more , Ali F, Sun J, Kou J
Anticancer Drugs · 2026 Feb · PMID 41191614 · Full text
KRAS -mutant non-small cell lung cancer (NSCLC) remains a major therapeutic challenge due to the paucity of effective targeted agents. Although covalent KRAS^G12C inhibitorsi such as sotorasib and adagrasib have demonstr...
KRAS -mutant non-small cell lung cancer (NSCLC) remains a major therapeutic challenge due to the paucity of effective targeted agents. Although covalent KRAS^G12C inhibitorsi such as sotorasib and adagrasib have demonstrated clinical activity, pooled analyses indicate only modest response rates and short progression-free survival, with no effective options for non-G12C subtypes. This highlights the need for novel therapeutic strategies with broader efficacy and improved durability. We evaluated the antiproliferative effects of SP09, a novel benzoin-Schiff base derivative, in KRAS -mutant (A549, H460) and EGFR -mutant (PC9) NSCLC cells, as well as normal lung cells. Cell viability, colony formation, and cell cycle distribution were assessed, and the involvement of the liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling axis was examined by western blot. SP09 selectively inhibited the proliferation of KRAS -mutant NSCLC cells (IC 50 ≈ 29 µM) with minimal toxicity to normal lung cells. Treatment induced G2/M arrest via downregulation of cyclin B1 and upregulation of p21. Mechanistically, SP09 activated the LKB1/AMPK pathway and suppressed mTOR signaling, leading to inhibition of downstream effectors, including P70S6K, S6, and sterol regulatory element-binding protein 1 (SREBP1). SP09 exerts potent and selective antiproliferative effects in KRAS -mutant NSCLC through dual regulation of cell cycle and metabolic signaling pathways. Given the restricted efficacy and rapid resistance associated with current KRAS -targeted therapies, our data highlight SP09 as a promising candidate for further preclinical development with potential translational value in KRAS -driven NSCLC.
Comparative efficacy and safety of S-1 plus oxaliplatin with sintilimab vs. paclitaxel-S-1-oxaliplatin and docetaxel-oxaliplatin-5-fluorouracil as first-line therapy for advanced gastric cancer.
Wang Y, Ma B, Zhang C … +7 more , Wang Y, Pan T, Zhao C, Cai B, Yu P, Guo B, Ma J
Anticancer Drugs · 2026 Apr · PMID 41191583 · Full text
This study compared the efficacy and safety of S-1 + oxaliplatin (SOX) plus sintilimab, albumin-bound paclitaxel + oxaliplatin (P-SOX), and docetaxel + oxaliplatin + 5-fluorouracil (DOF) as neoadjuvant regimens for advan...
This study compared the efficacy and safety of S-1 + oxaliplatin (SOX) plus sintilimab, albumin-bound paclitaxel + oxaliplatin (P-SOX), and docetaxel + oxaliplatin + 5-fluorouracil (DOF) as neoadjuvant regimens for advanced gastric cancer. We retrospectively analyzed 289 patients who received neoadjuvant and adjuvant chemotherapy followed by standard D2 radical gastrectomy (SOX + sintilimab, n = 81; P-SOX, n = 128; DOF, n = 80). Patients were randomly divided 7 : 3 into training and validation sets. Short-term efficacy, long-term outcomes, and adverse events were evaluated, and predictors of progression-free survival (PFS) were explored. The objective response rate of SOX + sintilimab was 91.36% by tumor regression grade (TRG) and 70.37% by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), numerically higher than P-SOX (88.38 and 59.20%) and DOF (86.25 and 57.50%) without significance (TRG, P = 0.587; RECIST 1.1, P = 0.178). Median overall survival (OS) was 32 months [95% confidence interval (CI): 30.00-not reached] with SOX + sintilimab, superior to P-SOX (28 months; 95% CI: 26.00-31.00) and DOF (26 months; 95% CI: 23.00- 32.00) ( P = 0.007). Median PFS was 30 months (95% CI: 27.00-33.00) for SOX + sintilimab, 25 months (95% CI: 22.00-26.00) for P-SOX, and 22.5 months (95% CI: 19.00-26.00) for DOF ( P = 0.096). Common adverse events included grade 1-2 gastrointestinal reactions, peripheral neurotoxicity, and alopecia, with good tolerability. SOX plus sintilimab achieved the most favorable OS with comparable safety.
Unlocking the role of prostate transmembrane androgen inducible protein 1 in gemcitabine resistance: modulation of P38-mitogen-activated protein kinase/C-C motif chemokine ligand 2 and M2 macrophage polarization in bladder cancer.
Yang G, Zhu X, Wei W … +1 more , Yin X
Anticancer Drugs · 2026 Jan · PMID 41185118 · Publisher ↗
Bladder cancer (BLCA) is a highly aggressive malignancy, with chemotherapy resistance being a significant factor in treatment failure. In the tumor microenvironment, M2 macrophage polarization is essential for immune sup...
Bladder cancer (BLCA) is a highly aggressive malignancy, with chemotherapy resistance being a significant factor in treatment failure. In the tumor microenvironment, M2 macrophage polarization is essential for immune suppression and treatment resistance. Key genes linked to M2 macrophage polarization and gemcitabine resistance in BLCA are examined in this work, along with possible underlying processes. Bioinformatics analyses were performed to identify differentially expressed genes in BLCA. Key hub genes related to M2 macrophage polarization and gemcitabine resistance were identified using various bioinformatics tools, including Cibersort, weighted gene coexpression network analysis, and gene set enrichment analysis. The effects of prostate transmembrane androgen inducible protein 1 (PMEPA1) silencing on cell viability, gemcitabine resistance, and macrophage polarization were further assessed using reverse transcription-quantitative PCR, Western blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, ELISA, and flow cytometry. Bioinformatics analysis revealed that PMEPA1 is a core gene associated with M2 macrophage polarization and gemcitabine resistance. Knockdown of PMEPA1 in BLCA cell lines reduced cell viability and enhanced gemcitabine sensitivity. Silencing of PMEPA1 also promoted M1 macrophage polarization while decreasing M2 macrophage polarization, as shown by the downregulation of cluster of differentiation (CD) 163 + and upregulation of CD86 + . Mechanistically, PMEPA1 regulated the P38-mitogen-activated protein kinase (MAPK)/C-C motif chemokine ligand 2 (CCL2) axis, leading to M2 macrophage polarization. Our findings suggest that PMEPA1 plays a crucial role in regulating M2 macrophage polarization and gemcitabine resistance in BLCA by activating the P38-MAPK/CCL2 signaling pathway.
Collagen I is the effective therapeutic target for treating desmoid tumors.
Lee Y, Kim Y, Lee C … +2 more , Kim TI, Cho YH
Anticancer Drugs · 2026 Mar · PMID 41184240 · Publisher ↗
Desmoid tumors, known as aggressive fibromatosis, are derived from connective tissues, and local invasion is usually observed. Despite intensive efforts have been performed to investigate the novel anticancer agents in d...
Desmoid tumors, known as aggressive fibromatosis, are derived from connective tissues, and local invasion is usually observed. Despite intensive efforts have been performed to investigate the novel anticancer agents in desmoid tumors, effective clinical management for treating desmoid tumors has not been developed yet. Additionally, the molecular mechanisms involved in the tumorigenesis of desmoid tumors have not been elucidated. In this study, given the frequent mutations of Wnt components and loss of function mutations in Trp53 in desmoid tumors, we developed the mouse models harboring Apc mutation with/without Trp53 knockout , Apc1638N/+ , and Apc1638N/+/Trp53-/- , respectively. We then established two primary cells derived from desmoid tumors in Apc1638N/+ and Apc1638N/+/Trp53-/- . Next, we have screened 3120 chemicals from a Food and Drug Administration-approved chemical library and identified halofuginone hydrobromide (HH), a collagen I-targeting compound, as exhibiting the most significant growth inhibition effects on Apc1638N/+ and Apc1638N/+/Trp53-/- desmoid tumor cells. Notably, HH also showed dramatic anticancer effects on colorectal cancer cells and mouse tumor organoids derived from intestinal tumors ( Apc1638N/+ ). Taken together, targeting collagen I is an effective therapeutic strategy for treating desmoid tumors and colorectal cancer patients.
9-Methoxycamptothecin induces proliferating cell nuclear antigen associated factor 15 mediated proliferation inhibition, DNA damage, and apoptosis in melanoma cells.
Ji Y, Li C, Hao H … +5 more , Liu Y, Mao Y, Zhang Y, Guo L, Shi S
Anticancer Drugs · 2026 Feb · PMID 41176789 · Publisher ↗
Melanoma is one of the most lethal forms of skin cancer, driving continuous research efforts to discover effective therapeutic strategies. Phytochemicals are promising for antimelanoma drug development because of their m...
Melanoma is one of the most lethal forms of skin cancer, driving continuous research efforts to discover effective therapeutic strategies. Phytochemicals are promising for antimelanoma drug development because of their multitarget bioactivities. 9-Methoxycamptothecin (MCPT), a plant-origin compound, has demonstrated potent anticancer activity against various human cancers; however, its inhibitory effects on melanoma and the underlying molecular mechanisms remain incompletely understood. In this research, human melanoma cell lines (A375, SKMEL28) were treated with MCPT. Cell proliferation was evaluated using MTT and clonogenic assays. Cell cycle and apoptosis were assessed by flow cytometry. The MCPT-induced DNA damage in melanoma cells was observed via immunofluorescence staining of γ-H2AX. Protein expression was analyzed by western blotting. Proliferating cell nuclear antigen associated factor 15 (PAF15) was overexpressed via lentiviral transduction to evaluate its functional role in MCPT response. The antimelanoma effect of MCPT in vitro was studied in BALB/c nude mice bearing subcutaneous tumors from A375 cells. The results showed that MCPT suppressed melanoma cell proliferation via inducing the G2/M phase cell cycle arrest. Meanwhile, MCPT induces caspase-dependent apoptosis and DNA damage in melanoma cells. In vivo , MCPT effectively inhibited the growth of melanoma xenografts. Crucially, these MCPT-mediated effects were partly rescued by exogenous PAF15 overexpression. In conclusion, MCPT exerts antimelanoma effects by inhibiting proliferation, inducing cell cycle arrest, DNA damage, and apoptosis. Importantly, these effects are critically mediated through the downregulation of PAF15.
Multimodal treatment with thiotepa, bevacizumab, teniposide, and tunlametinib in a patient with neurofibromatosis type 1-associated oligodendroglioma: a rare case report.
Zhou S, Chen Y, Gao G … +3 more , Pan X, Sun P, Tao R
Anticancer Drugs · 2026 Apr · PMID 41176787 · Publisher ↗
Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder associated with central nervous system gliomas, most frequently optic pathway gliomas; however, oligodendrogliomas in the setting of NF1 are exceedin...
Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder associated with central nervous system gliomas, most frequently optic pathway gliomas; however, oligodendrogliomas in the setting of NF1 are exceedingly rare, with no prior documented cases and no established treatment strategies to date. A 53-year-old female with NF1-associated oligodendroglioma experienced multiple recurrences following surgery, radiotherapy, chemotherapy, and targeted therapy. Upon further disease progression, she was treated with a novel combination of thiotepa, bevacizumab, teniposide, and the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor tunlametinib. After one treatment cycle, the patient achieved a marked reduction in tumor volume, consistent with a complete response (CR). She subsequently completed eight additional cycles of the regimen and has maintained CR. The treatment was well-tolerated, with manageable grade 3 myelosuppression controlled by supportive care. As of June 2025, the patient has achieved a CR with a progression-free survival of 9 months before experiencing disease recurrence. This rare case of NF1-associated oligodendroglioma was managed with thiotepa, bevacizumab, teniposide, and tunlametinib, highlighting the potential of MEK inhibition in NF1-related gliomas.
Initial stage analysis of tislelizumab in combination with chemotherapy for patients with advanced HIV-positive non-small-cell lung cancer: a comparative clinical trial.
Quan Y, Li H, Liang Z … +2 more , Shen J, Hu Y
Anticancer Drugs · 2026 Apr · PMID 41176784 · Full text
Immune checkpoint inhibitors (ICIs) are a standard treatment for advanced non-small-cell lung cancer (NSCLC), but limited data exist regarding their use in patients with HIV-positive. This study evaluated the efficacy an...
Immune checkpoint inhibitors (ICIs) are a standard treatment for advanced non-small-cell lung cancer (NSCLC), but limited data exist regarding their use in patients with HIV-positive. This study evaluated the efficacy and safety of ICI-based therapy in this population. In this single-center, comparative study, 18 patients with treatment-naive advanced NSCLC with HIV (experimental group) and 40 HIV-negative controls (control group) received 4-6 cycles of tislelizumab plus platinum-based chemotherapy, followed by tislelizumab maintenance until disease progression or unacceptable toxicity. A higher incidence of tuberculosis was observed in the experimental group compared with the control group (33.3 vs. 20.0%). The objective response rate was 77.8% [95% confidence interval (CI): 56.5-99.1] in the experimental group and 77.5% (95% CI: 64-91) in the control group ( P = 0.981). The 6-month progression-free survival rate was 83.3% (95% CI: 64.3-99.9) for the experimental group and 82.5% (95% CI: 70.2-94.8) for the control group ( P = 0.227). The 6-month overall survival rate was 88.9% (95% CI: 72.8-99.9) in the experimental group and 97.5% (95% CI: 92.4-99.9) in the control group ( P = 0.192). The incidences of grade 3 or higher adverse events were 38.9 and 32.5% in the experimental and control groups, respectively. One patient in the experimental group died due to a serious opportunistic infection. Immunotherapy combined with chemotherapy showed comparable efficacy and safety in patients with advanced NSCLC irrespective of HIV status. Patients with HIV-positive had a higher tendency for opportunistic infections, including tuberculosis.
Locoregional and symptomatic response to neoadjuvant dual HER2 blockade with chemotherapy in HER2-positive breast cancer: a pilot study.
Chowdhary GS, Nayyar A, Vasudevan S … +1 more , Kaur K
Anticancer Drugs · 2026 Apr · PMID 41176781 · Publisher ↗
Dual HER2 blockade with trastuzumab and pertuzumab in combination with chemotherapy has improved pathological complete response (pCR) rates in HER2-positive breast cancer in randomized trials. However, real-world pilot d...
Dual HER2 blockade with trastuzumab and pertuzumab in combination with chemotherapy has improved pathological complete response (pCR) rates in HER2-positive breast cancer in randomized trials. However, real-world pilot data on locoregional and symptomatic outcomes in patients receiving this regimen before surgery are limited. This was a prospective pilot study including 20 patients with HER2-positive breast cancer treated with neoadjuvant trastuzumab, pertuzumab, and chemotherapy. Patients were assessed clinically and radiologically at baseline and following completion of neoadjuvant therapy. Primary endpoints were locoregional response (tumor shrinkage, nodal downstaging, and operability) and symptomatic improvement (pain, heaviness, and nipple/skin changes). All patients subsequently underwent definitive surgery. Median age was 46 years (range 32-65). Most patients presented with locally advanced disease, and 70% had palpable axillary nodes. Following neoadjuvant therapy, the overall clinical response rate was 85%, with 25% achieving complete clinical response and 60% partial response. Median tumor reduction was approximately 50%. Nodal downstaging was seen in 60%, with complete nodal response in 30%. Symptomatic improvement was reported in 80% for pain, 70% for heaviness, and 60% for skin/nipple changes. All patients proceeded to surgery, and pCR was achieved in 25%. The regimen was well tolerated, with no major cardiac events or treatment-related mortality. Neoadjuvant dual HER2 blockade with chemotherapy is feasible in HER2-positive breast cancer, achieving high clinical response rates, meaningful symptomatic improvement, and acceptable safety in this pilot study. These findings provide early single-center, prospective pilot evidence supporting dual HER2-targeted neoadjuvant therapy, with implications for operability and patient-centered outcomes. Larger multicentre studies are needed to validate these results.
PLCG2 promotes cell survival and mitophagy of small cell lung cancer via regulating VCP.
Jiang J, Zhu J, Xiao Y … +1 more , Gan L
Anticancer Drugs · 2026 Jan · PMID 41176779 · Publisher ↗
Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer that is characterized by rapid growth. PLCG2 is an enzyme that plays a crucial role in intracellular signal transduction pathways. This study aims...
Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer that is characterized by rapid growth. PLCG2 is an enzyme that plays a crucial role in intracellular signal transduction pathways. This study aims to discover the role of PLCG2 in SCLC and the underlying mechanism. Relative expression of PLCG2 was detected by reverse transcription-quantitative PCR and Western blot. Cell viability, proliferation, and apoptosis were assessed by cell counting kit-8, colony formation, and flow cytometry assays. Mitophagy-related protein levels were analyzed by Western blot. RNA immunoprecipitation and dual-luciferase reporter assays were used to analyze the interaction between PLCG2 and VCP . A xenograft mouse model was established to analyze the role of PLCG2 in vivo . Results showed that PLCG2 was upregulated in SCLC tissues and cells, with high diagnostic potential. Besides, PLCG2 deficiency inhibited cell survival and mitophagy and promoted apoptosis in SCLC cells. In addition, PLCG2 interacted with VCP , and VCP overexpression reversed the inhibitory effects of PLCG2 silencing. In vivo , PLCG2 silencing suppressed SCLC tumor growth. In conclusion, PLCG2 is a promising biomarker for SCLC diagnosis and might be a potential therapeutic target, with its interaction with VCP playing a role in SCLC cell survival and mitophagy.
Anti-CD19 antibody tafasitamab therapy for relapsed or refractory diffuse large B-cell lymphoma: a case series.
You J, Chen W, Yan Z … +8 more , Tian D, Yi H, Feng Y, Zhang M, Xing T, Wang Z, Zhao W, Xu P
Anticancer Drugs · 2026 Feb · PMID 41176775 · Publisher ↗
Tafasitamab, an anti-CD19 mAb, has demonstrated promising efficacy in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) in Western populations, but its use in Chinese patients has not been reported. This c...
Tafasitamab, an anti-CD19 mAb, has demonstrated promising efficacy in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) in Western populations, but its use in Chinese patients has not been reported. This case series reports the use of tafasitamab in four Chinese patients with R/R DLBCL. Four patients with R/R DLBCL were treated at the Department of Hematology, Hainan Hospital of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. All patients had previously received rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. After treatment with tafasitamab and lenalidomide, two patients with primary refractory disease, one achieved a partial response and another had stable disease. One patient who relapsed after autologous stem-cell transplantation received tafasitamab plus lenalidomide and a Bruton tyrosine kinase (BTK) inhibitor and showed remarkable tumor reduction in all sites except for the lymph nodes in the left inguinal region. One patient who relapsed after second-line therapy achieved complete remission with tafasitamab monotherapy. Tafasitamab-based treatment was well-tolerated, with the most common adverse event being neutropenia. Our real-world experience first suggests that tafasitamab-based flexible treatment may be a potential treatment option for Chinese patients with R/R DLBCL, supporting the need for further investigation into its efficacy and safety in Chinese patients, with a particular focus on exploring directions such as combinations with BTK inhibitors.
Successful treatment with erlotinib plus ramucirumab in a patient with non-small-cell lung cancer harboring EGFR exon 20 insertion mutation.
Nakashima K, Yamaoka K, Umeda Y … +1 more , Waseda Y
Anticancer Drugs · 2026 Feb · PMID 41176685 · Publisher ↗
As epidermal growth factor receptor ( EGFR ) exon 20 insertion mutations generally result in poor sensitivity to EGFR -tyrosine kinase inhibitors (TKIs), the administration of EGFR -TKIs is not recommended in non-small-c...
As epidermal growth factor receptor ( EGFR ) exon 20 insertion mutations generally result in poor sensitivity to EGFR -tyrosine kinase inhibitors (TKIs), the administration of EGFR -TKIs is not recommended in non-small-cell lung cancer (NSCLC). Nonetheless, EGFR exon 20 A763_Y763insFQEA, a genotype of EGFR exon 20 insertion mutations, has some sensitivity to EGFR -TKIs. However, the therapeutic effects of EGFR -TKIs alone for EGFR exon 20 A763_Y763insFQEA are insufficient compared to those for common EGFR mutations. Therefore, more effective treatment options are required for this mutation. Herein, we present a case in which treatment with erlotinib plus ramucirumab led to a complete response and progression-free survival of 13 months in a 79-year-old man with advanced NSCLC harboring EGFR exon 20 A763_Y763insFQEA. This case suggests that this regimen should be considered as an effective treatment option for such patients.
Identifying novel triazole-containing histone deacetylase 1 antitumor inhibitors through molecular simulations and ADME/T profiling.
Tuo Y, Li C, Wan Q … +3 more , Tang Y, Wang Y, Chen W
Anticancer Drugs · 2026 Jan · PMID 41176684 · Publisher ↗
Histone deacetylase 1 (HDAC1), a pivotal epigenetic modulator, is critically involved in oncogenesis and serves as a promising target for anticancer drug discovery. In this study, 59 reported HDAC1 inhibitors were utiliz...
Histone deacetylase 1 (HDAC1), a pivotal epigenetic modulator, is critically involved in oncogenesis and serves as a promising target for anticancer drug discovery. In this study, 59 reported HDAC1 inhibitors were utilized to establish robust three-dimensional quantitative structure-activity relationship models for designing novel triazole-containing derivatives with optimized bioactivity and pharmacokinetic profiles. Comparative molecular field analysis ( n = 9, R2 = 0.966, q2 = 0.781) and comparative molecular similarity index analysis ( n = 6, R2 = 0.945; q2 = 0.778) confirmed the predictive reliability of these models. On the basis of the contour maps analysis, the key structural modification sites were determined, and seven promising analogs were reasonably designed. These candidates showed good drug-likeness in ADME/T profiling and formed stable complexes with HDAC1 in molecular simulations, underscoring their promising inhibitory potential. Our study provided a strategic framework for the discovery of HDAC1 drugs and identified promising leads for cancer therapeutics.
Histone lactylation promoted colorectal cancer progression by enhancing tumor necrosis factor transcription and served as a diagnostic biomarker.
Li S, Shi X, Zhou X
Anticancer Drugs · 2026 Mar · PMID 41176660 · Publisher ↗
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, with unmet needs for early diagnostic biomarkers and therapeutic targets. Recent studies highlight the role of histone lactylation (H3...
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, with unmet needs for early diagnostic biomarkers and therapeutic targets. Recent studies highlight the role of histone lactylation (H3K18la) in modulating gene expression and tumor progression. Its specific mechanisms in CRC, however, remain poorly understood. This study analyzed 60 CRC patients to evaluate H3K18la levels in tumor and adjacent nontumor tissues via Western blot and correlated them with clinical parameters. CRC cell lines were treated with sodium lactate (Nala) to investigate H3K18la's regulatory effects on tumor necrosis factor (TNF) transcription. Mechanistic insights were derived from RNA sequencing, chromatin immunoprecipitation (ChIP) assays, luciferase reporter assays, and RT-qPCR. Diagnostic potential was assessed using receiver operating characteristic curve analysis. H3K18la levels were significantly elevated in CRC tissues compared with adjacent tissues and exhibited high diagnostic accuracy. High H3K18la expression correlated with larger tumor size and advanced american joint committee on cancer (AJCC) stages. Furthermore, H3K18la levels positively correlated with serum carcinoembryonic antigen and carbohydrate antigen 19-9. Nala treatment enhanced H3K18la enrichment at the TNF promoter, upregulating TNF transcription in CRC cells. Mechanistically, H3K18la directly activated TNF promoter activity, as demonstrated by luciferase reporter assays and ChIP analysis. In conclusion, H3K18la serves as a promising diagnostic biomarker for CRC, with strong correlations to tumor progression. Its oncogenic role is mediated, at least partially, through transcriptional activation of TNF. These findings position H3K18la as a novel therapeutic target for CRC and underscore its potential for early detection and personalized treatment strategies.
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