Anti-Cancer DrugsPub Date : 2025-07-01Epub Date: 2025-05-07DOI: 10.1097/CAD.0000000000001708
Michael R Booth, Laurence Booth, Jane L Roberts, Cameron West, Paul Dent
{"title":"GZ17-6.02 interacts with carboplatin and etoposide to kill neuroblastoma cells.","authors":"Michael R Booth, Laurence Booth, Jane L Roberts, Cameron West, Paul Dent","doi":"10.1097/CAD.0000000000001708","DOIUrl":"10.1097/CAD.0000000000001708","url":null,"abstract":"<p><p>The biology of GZ17-6.02 alone and more so in combination with either of the standard-of-care agents etoposide or carboplatin killed MYCN overexpressing neuroblastoma (NB) cells is unknown. The methods involved in this study are in-cell immunoblotting, trypan blue exclusion, plasmid and siRNA transfection, assessment of autophagy using a plasmid expressing LC3-GFP-RFP. GZ17-6.02 (602) comprises, by mass, a ratio of curcumin (1.0), harmine (1.3), and isovanillin (7.7). In tumors dosed with 602, the ratio becomes curcumin (1.0), harmine (16), and isovanillin (6.1) (602NR). GZ17-6.02 activated ATM, AMPK, ULK1, ATG13, and PERK and inactivated ERBB1, ERBB2, ERBB3, ERBB4, AKT, mTORC1, mTORC2, SRC, NFκB, YAP, and eIF2α. 602 enhanced autophagosome formation and autophagic flux that was amplified when it was combined with etoposide or carboplatin. Compared with 602, 602NR caused significantly greater autophagosome formation that was also amplified when in combination with chemotherapy and which was reduced ~40% by knockdown of ATM or AMPKα and abolished by knockdown of Beclin1 or ATG5. Knockdown of ATM or AMPKα significantly reduced tumor cell death caused by 602 of 602NR, whereas endoplasmic reticulum stress (eIF2α) and macroautophagy (Beclin1, ATG5) were more effective at maintaining tumor cell survival. Combined knockdown of Beclin1 and the death receptor CD95 almost abolished the antitumor actions of 602 and 602NR. 602, and more so 602NR, kills MYCN NB cells and interacts with standard-of-care chemotherapeutics to cause further killing via autophagy and death receptor signaling.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"478-488"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2025-07-01Epub Date: 2025-02-18DOI: 10.1097/CAD.0000000000001706
Haijun Ding, Xuedian Tang, Wenjun Tang
{"title":"Effect of adjuvant chemotherapy with toad venom injection in the treatment of intermediate and advanced colon cancer and its effect on cellular immunity, PTEN, and PI3k.","authors":"Haijun Ding, Xuedian Tang, Wenjun Tang","doi":"10.1097/CAD.0000000000001706","DOIUrl":"10.1097/CAD.0000000000001706","url":null,"abstract":"<p><p>The objective of this study is to explore the effect of adjuvant chemotherapy with toad venom injection in patients with intermediate and advanced colon cancer, in order to provide new reference drugs for clinical treatment. Prospectively, 148 patients with mid-stage to late-stage colon cancer in our hospital from January 2021 to May 2023 were selected for the study and randomly divided into two groups of 74 cases each. The control group was treated with FOLFOX4 chemotherapy, and the observation group was treated with four consecutive chemotherapy cycles based on the control group combined with toad venom injection. The treatment effects, adverse reactions, quality of life improvement rate, prognosis and cellular immune indexes [natural killer (NK) cells, CD4 + /CD8 + , CD4 + , CD3 + ], phosphatase tensin gene ( PTEN ), phosphatidylinositol-3-kinase (PI3k), and serine threonine protein kinase (pAKT) protein expression before and after treatment were counted in the two groups. The total effective rate of treatment in the observation group was 58.11% (43/74) after four cycles of chemotherapy, which was higher than that in the control group of 41.89% (31/74) ( P < 0.05). After two cycles of chemotherapy and four cycles of chemotherapy, PTEN , CD4 + /CD8 + , CD4 + , CD3 + , and NK cells in peripheral blood were higher in the observation group than in the control group, and PI3k and pAKT were lower than in the control group ( P < 0.05). There was no statistically significant difference in the rate of adverse reactions in the observation group compared with the control group ( P > 0.05); the improvement rate of quality of life in the observation group was better than that in the control group after four chemotherapy cycles of treatment ( P < 0.05); the survival rate was 75.00% (54/72) in the observation group compared with 54.29% (38/70) in the control group at 1-year follow-up. Toad venom injection adjuvant chemotherapy is effective in treating patients with intermediate and advanced colon cancer, which can upregulate PTEN level, inhibit PI3k and AKT expression, and improve immune function and quality of life of patients, thus improving prognosis.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"495-500"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-term survival of an ALK fusion lung adenocarcinoma patient with high mutation burden and microsatellite instability high: a case report.","authors":"Yanrong Guo, Jinfang Zhai, Yanli Yang, Qin Wei, Shengshu Li, Rujie Huo, Guoping Tong, Enwei Xu, Yan Chen, Songyan Han, Deyi Chen","doi":"10.1097/CAD.0000000000001693","DOIUrl":"10.1097/CAD.0000000000001693","url":null,"abstract":"<p><p>Immune checkpoint blockage (ICB) therapy has shown minimal effectiveness in anaplastic lymphoma kinase (ALK)-positive nonsmall cell lung cancer (NSCLC) regardless of Programmed death-ligand 1 expression. ALK fusion accompanied by mismatch repair deficiency or microsatellite instability-high (MMRd/MSI-H) and high tumor mutation burden (TMB-H) are extremely rare in NSCLC, and the efficacy of ALK inhibitors or ICB-based therapies is unclear. Here, we report the case of a 60-year-old female patient with metastatic lung adenocarcinoma accompanied by EML4-ALK fusion, TMB-H, MMRd/MSI-H, and pathogenic mutations in TP53, MLH1, and STK11. The patient experienced progression on initial iruplinalkib and subsequent alectinib therapy within 5 months. After the failure of third-line therapy with cisplatin-pemetrexed combined with bevacizumab, she received sintilimab plus anlotinib which led to a progression-free survival of 6.5 months. She received sintilimab combined with albumin-paclitaxel plus carboplatin and achieved partial response after 6 months. She developed adverse events after one cycle of sintilimab plus albumin-paclitaxel treatment. Then she was continued with sintilimab plus anlotinib as a maintenance therapy due to intolerance to chemotherapy. After progression on ICB-based therapy, the patient was treated with lorlatinib and still under follow-up with overall survival of more than 3 years. Our findings highlight the therapeutic potential of ICB-based regimens in patients with MSI-H and ALK-rearranged NSCLC.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"427-431"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2025-06-01Epub Date: 2025-02-04DOI: 10.1097/CAD.0000000000001697
Chang Xu, Jing Ren, Changqing Liu, Yi Gai, Xiangyu Cheng, Yusheng Wang, Guangyu Wang
{"title":"Comparative efficacy of cetuximab combined with FOLFOX or CAPEOX in first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer: a multicenter case-control study.","authors":"Chang Xu, Jing Ren, Changqing Liu, Yi Gai, Xiangyu Cheng, Yusheng Wang, Guangyu Wang","doi":"10.1097/CAD.0000000000001697","DOIUrl":"10.1097/CAD.0000000000001697","url":null,"abstract":"<p><p>FOLFOX combined with cetuximab is a recommended first-line treatment regimen for RAS/BRAF wild-type metastatic colorectal cancer (mCRC). CAPEOX combined with cetuximab differs from the FOLFOX regimen by using oral capecitabine instead of continuous infusion of fluorouracil, offering greater convenience and cost-effectiveness with higher patient acceptance. However, the comparative efficacy of these two regimens remains debatable, necessitating further evidence to explore any differences in their efficacy. This study collected medical records of mCRC patients who were treated with CAPEOX or FOLFOX combined with cetuximab from 1 October 2021 to 16 October 2023 at Harbin Medical University Cancer Hospital and the First Hospital of Shanxi Medical University. Eligible patients were selected based on inclusion criteria and followed up through the hospital's follow-up system and telephone interviews. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were used to assess patients' progression-free survival (PFS) and overall survival (OS). A total of 71 eligible patients were enrolled in this study; 43 patients received CAPEOX combined with cetuximab (Group A, n = 43), and 28 patients received FOLFOX combined with cetuximab (Group B, n = 28). The two groups achieved similar median PFS (mPFS) and median OS (mOS), with mPFS of 18 months and 12 months, respectively ( P = 0.23), and mOS of 33 months and 20 months, respectively ( P = 0.21), with no statistically significant differences. The results of this study demonstrated that CAPEOX combined with cetuximab is an equally viable option for first-line treatment of RAS/BRAF wild-type mCRC as FOLFOX combined with cetuximab.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"383-393"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2025-06-01Epub Date: 2025-02-25DOI: 10.1097/CAD.0000000000001701
Tingfei Tan, Siyu Yuan, Weiwei Chu, Jiemei Jiang, Meiling Chen, Quan Xia, Junping Wang
{"title":"Low-dose anlotinib plus immune checkpoint inhibitors offers better efficacy and safety in advanced non-small cell lung cancer treatment.","authors":"Tingfei Tan, Siyu Yuan, Weiwei Chu, Jiemei Jiang, Meiling Chen, Quan Xia, Junping Wang","doi":"10.1097/CAD.0000000000001701","DOIUrl":"10.1097/CAD.0000000000001701","url":null,"abstract":"<p><p>The combination of anlotinib with immune checkpoint inhibitors (ICIs) has become a common treatment modality in clinical practice. However, the optimal dose of anlotinib to use remains unclear. We collected patients with advanced non-small cell lung cancer (NSCLC) who received programmed cell death-1 blockade combined with different dose of anlotinib as second-line or later line therapy. Subsequently, the efficacy and safety of the combination therapy as well as subgroup analyses of different doses of anlotinib were analyzed. Cox regression was performed to analyze significant factors correlated with progression-free survival (PFS) and overall survival (OS). A total of 50 eligible patients with NSCLC who received anlotinib combined with ICIs therapy were included, of which 27 received low-dose anlotinib (8 mg), and 23 were administered high-dose anlotinib (12 mg). The median PFS (mPFS) and the median OS (mOS) for all patients were 8.3 months [95% confidence interval (CI): 6.3-10.3] and 17.6 months (95% CI: 16.5-18.7), respectively. Subgroup analyses showed that patients treated with 8 mg of anlotinib plus ICIs had significantly longer mPFS than those treated with 12 mg of anlotinib plus ICIs (8.7 vs 6.7 months, P = 0.016). The overall incidence of adverse events was 68.0%, and the most common adverse events of all grades were hypertension. Meanwhile, the incidence of adverse events was higher for 12 mg of anlotinib plus ICIs than that of 8 mg of anlotinib plus ICIs (82.6 vs 55.6%, P = 0.041). Low-dose anlotinib in combination with ICIs for advanced NSCLC may be an effective and well-tolerated option.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"408-414"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2025-06-01Epub Date: 2025-01-29DOI: 10.1097/CAD.0000000000001698
Siyuan Li, Yanqin Zhang, Rong Yang, Qingfan Yang, Shuangyan Han, Dan Li, Zhenhua Zhang, Qinglian Wen
{"title":"A phase II study of anlotinib as first-line maintenance therapy for advanced ovarian cancer.","authors":"Siyuan Li, Yanqin Zhang, Rong Yang, Qingfan Yang, Shuangyan Han, Dan Li, Zhenhua Zhang, Qinglian Wen","doi":"10.1097/CAD.0000000000001698","DOIUrl":"10.1097/CAD.0000000000001698","url":null,"abstract":"<p><p>Anlotinib, a tyrosine kinase inhibitor, has shown encouraging antitumor activity in platinum-resistant/refractory ovarian cancer. The efficacy of anlotinib as maintenance therapy in advanced ovarian cancer remains unclear. Therefore, we designed this study to evaluate the efficacy and safety of anlotinib maintenance therapy following first-line treatment with paclitaxel and platinum-based chemotherapy in advanced ovarian cancer. In this single-arm, phase II clinical trial, patients with newly diagnosed advanced ovarian cancer were received anlotinib monotherapy as maintenance therapy once after a response to platinum-based chemotherapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival. From April 2020 to June 2021, 24 patients were enrolled in this study. The median follow-up was 40.17 months (interquartile range, 32.40-47.93 months). Of 21 patients with efficacy value, the median progression-free survival and median overall survival were 15.8 months (95% confidence interval, 6.8-24.8 months) and 43.8 months (95% confidence interval, 25.45-62.15 months). The quality-adjusted progression-free survival was 14.4 months and there were no observed treatment-related deaths or serious treatment-emergent adverse events, demonstrating the safety of anlotinib in maintenance therapy. Anlotinib shows significant potential as a first-line maintenance therapy for advanced ovarian cancer, extending survival and providing a reliable treatment option.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"394-400"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2025-06-01Epub Date: 2025-02-06DOI: 10.1097/CAD.0000000000001704
Jun Wei, Yuexuan Qin, Luwen Zhang, Xiaobing Gong
{"title":"Combined protein and transcriptomics identifies DCTPP1 as a putative biomarkers for predicting immunotherapy responsiveness in gastric cancer patients.","authors":"Jun Wei, Yuexuan Qin, Luwen Zhang, Xiaobing Gong","doi":"10.1097/CAD.0000000000001704","DOIUrl":"10.1097/CAD.0000000000001704","url":null,"abstract":"<p><p>This study aimed to screen the changes after overexpression of dCTP pyrophosphatase 1 (DCTPP1) in human gastric adenocarcinoma cells (AGS) cells by proteome and transcriptome sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to explore the functional significance of the differentially expressed DCTPP1 in gastric cancer (GC). Cell Counting Kit-8 (CCK-8) assay was used to detect the proliferation of cells. Western blot was used to detect the expression of proteins. A total of 28 genes that were significantly associated with DCTPP1 overexpression and had prognostic value were screened by Cox regression analysis. The results of gene set enrichment analysis showed that the genomes of patients with subtype A exhibited significant enrichment in pathways such as DNA repair, pyrimidine synthesis, and glucose metabolism. The tumor immune dysfunction and exclusion and The Cancer Immunome Atlas databases showed that patients with type A GC were better candidates for immunotherapy than patients with type B GC. Furthermore, the CCK-8 assay indicated significantly enhanced proliferative activity after overexpressing DCTPP1 in AGS cells, corroborating the findings from the bioinformatic analysis. The data suggest a potential association between DCTPP1 expression and both the prognosis of GC patients and the efficacy of immunotherapy. These findings offer valuable insights for the potential optimization of therapeutic strategies in gastric cancer.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"415-426"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2025-06-01Epub Date: 2025-02-25DOI: 10.1097/CAD.0000000000001696
Zhu-Xia Jia, Bi-Tao Xiao, Jin Li, Xiao-Hui Cai, Wei Qin, Min Zhou, Xu-Zhang Lu
{"title":"BTK inhibitors enhance NKG2D ligand expression by regulating IL-10/STAT3 pathway in activated non-GCB diffuse large B-cell lymphoma cells.","authors":"Zhu-Xia Jia, Bi-Tao Xiao, Jin Li, Xiao-Hui Cai, Wei Qin, Min Zhou, Xu-Zhang Lu","doi":"10.1097/CAD.0000000000001696","DOIUrl":"10.1097/CAD.0000000000001696","url":null,"abstract":"<p><p>The aim of this study is to explore the role of the IL-10/STAT3 pathway in the upregulation of natural killer group 2, member D (NKG2D) ligands (MICA and ULBP2) induced by Bruton's tyrosine kinase (BTK) inhibitors in non-germinal center B-cell-like diffuse large B-cell lymphoma cells. The expression levels of NKG2D ligands and the IL-10/STAT3 pathway in SUDHL4, U2932, and OCI-LY3 cells were analyzed using western blotting. After stimulation of the B-cell receptor signaling pathway with IgM antibodies, the expression levels of NKG2D ligands, as well as IL-10 and phosphorylated STAT3 (p-STAT3) were significantly reduced. In contrast, treatment with ibrutinib produced effects opposite to those induced by IgM antibodies. Additionally, treatment of U2932 and OCI-LY3 cells with the STAT3 inhibitor (STAT3-IN-1) led to an increase in NKG2D ligand expression and a decrease in IL-10 levels. When IL-10 neutralizing antibodies were introduced, p-STAT3 levels decreased, and NKG2D ligand expression increased. Similar outcomes were observed when the BTK inhibitors ACP-196 and BGB-3111 were administered. Our findings suggest that the IL-10/STAT3 pathway plays a key role in the upregulation of NKG2D ligands induced by BTK inhibitors in U2932 and OCI-LY3 cells.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"374-382"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2025-06-01Epub Date: 2025-02-04DOI: 10.1097/CAD.0000000000001700
Carolina Alarcón-Payer, María Del Mar Sánchez Suárez, Alicia Martín Roldán, Alberto Jimnez Morales
{"title":"Association between nilotinib-induced hyperbilirubinemia and UGT1A1 polymorphisms in a chronic myeloid leukemia patient.","authors":"Carolina Alarcón-Payer, María Del Mar Sánchez Suárez, Alicia Martín Roldán, Alberto Jimnez Morales","doi":"10.1097/CAD.0000000000001700","DOIUrl":"10.1097/CAD.0000000000001700","url":null,"abstract":"<p><p>We present the case of a young woman diagnosed with chronic myeloid leukemia who began de-novo treatment with nilotinib, which led to increased plasma levels of total bilirubin and QT interval. An evaluation of the genetic profile of uridine diphosphate glucuronosyltransferase was made, as nilotinib inhibits the activity of this enzyme causing hyperbilirubinemia, with higher risk in slow metabolizers, such as those ones with *6/*6 genotype. This type of patient can be identified by genetic profiling, and adjustment in the dose of nilotinib could be made to avoid tyrosine kinase inhibitor switching.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"438-439"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Iruplinalkib for G1202R-mutant non-small cell lung cancer with anaplastic lymphoma kinase double fusion failed to alectinib: a case report.","authors":"Guangjian Yang, Jiaqi Hu, Runze Liu, Pei Li, Linke Yang, Xiaoyong Tang, Luokun Wang","doi":"10.1097/CAD.0000000000001695","DOIUrl":"10.1097/CAD.0000000000001695","url":null,"abstract":"<p><p>The novel and highly selective anaplastic lymphoma kinase ( ALK ) inhibitor iruplinalkib showed potent activity and manageable safety profiles in patients with ALK -rearranged non-small cell lung cancer (NSCLC). However, the evidence of iruplinalkib for uncommon ALK double fusion and secondary G1202R resistance mutation is limited. Here, we report a case of a 36-year-old male with metastatic NSCLC harboring uncommon TTC7A - ALK and EML4 - ALK double fusion. Alectinib as first-line therapy showed partial response, with a progression-free survival (PFS) of 20 months. When his disease progressed, the ALK secondary G1202R resistance mutation was identified. His metastatic paraesophageal lymph node decreased during iruplinalkib treatment, achieving an ongoing PFS benefit for 10 months. Treatment-related adverse events of iruplinalkib were grade 1 hypercholesterolemia and hypertriglyceridemia. The modeling simulation revealed that the G1202R mutation exerted little effect on the binding of iruplinalkib. Iruplinalkib showed potency to G1202R because of its unique chemical structure and removal of steric clashes, which might be a promising option for ALK -rearranged NSCLC patients with G1202R resistance mutation.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"432-437"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}