Anti-Cancer Drugs最新文献

{"title":"Holding the therapy in CLLp53: mechanisms to achieve durable responses.","authors":"Rodrigo Cantera, Tatiana Fernández-Barge, Jon Salmanton-García, Lucrecia Yáñez","doi":"10.1097/CAD.0000000000001653","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001653","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is a common leukemia, mainly affecting the elderly. Originating in the bone marrow, CLL involves the accumulation of B lymphocytes and progresses slowly, though 50-60% of patients will require therapy. At diagnosis, the presence of p53 protein aberrations, such as 17p deletion and TP53 mutation, arises in approximately one out of 10 patients. Even in the era of targeted therapies, these aberrations remain the most important prognostic factors. Current guidelines favor continuous BTK inhibitor therapy in patients with CLLp53, though adverse events and drug resistance may lead to discontinuation. Herein, we discuss the effects of B-cell receptor and BCL-2 inhibition, as well as the role of the immune system, in two elderly CLLp53 patients with prolonged responses to different therapies.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915973","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":"Machine learning-based integration develops a multiple programmed cell death signature for predicting the clinical outcome and drug sensitivity in colorectal cancer.","authors":"Chunhong Li, Yuhua Mao, Yi Liu, Jiahua Hu, Chunchun Su, Haiyin Tan, Xianliang Hou, Minglin Ou","doi":"10.1097/CAD.0000000000001654","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001654","url":null,"abstract":"<p><p>Tumorigenesis and treatment are closely associated with various programmed cell death (PCD) patterns. However, the coregulatory role of multiple PCD patterns in colorectal cancer (CRC) remains unknown. In this study, we developed a multiple PCD index (MPCDI) based on 19 PCD patterns using two machine learning algorithms for risk stratification, prognostic prediction, construction of nomograms, immune cell infiltration analysis, and chemotherapeutic drug sensitivity analysis. As a result, in the TCGA-COAD, GSE17536, and GSE29621 cohorts, the MPCDI can effectively distinguished survival outcomes in CRC patients and served as an independent factor for CRC patients. We then explored the immune infiltration landscape in two groups using the nine algorithms and found more overall immune infiltration in the high-MPCDI group. TIDE scores suggested that the increased immune evasion potential and immune checkpoint inhibition therapy may be less effective in the high-MPCDI group. Immunophenoscores indicated that anti-PD1, anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA4), and anti-PD1-CTLA4 combination therapies are less effective in the high-MPCDI group. In addition, the high-MPCDI group was more sensitive to AZD1332, Foretinib, and IGF1R_3801, and insensitive to AZD3759, AZD5438, AZD6482, Erlotinib, GSK591, IAP_5620, and Picolinici-acid, which suggests that the MPCDI can guide drug selection for CRC patients. As a new clinical classifier, the MPCDI can more accurately distinguish CRC patients who benefit from immunotherapy and develop personalized treatment strategies for CRC patients.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915974","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":"Pathological complete response achieved with FLOT chemotherapy in two patients with MSI-H esophagogastric junction and gastric adenocarcinoma.","authors":"Federica Cosso, Daniele Lavacchi, Luca Messerini, Vittorio Briganti, Francesca Castiglione, Marco Brugia, Valentina Berti, Sara Fancelli, Fabio Cianchi, Agnese Vannini, Serena Pillozzi, Lorenzo Antonuzzo","doi":"10.1097/CAD.0000000000001652","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001652","url":null,"abstract":"<p><p>Globally, more than 1 million new cases of gastric cancer were estimated in 2020, ranking fourth in cancer mortality. Currently although in resectable gastric cancer and esophagogastric junction (EGJ) adenocarcinoma a perioperative triplet chemotherapy regimen including a fluoropyrimidine, a platinum compound and docetaxel (FLOT) demonstrated a better overall survival, the survival rate is still very low, and a massive effort is still required to improve clinical prognosis. High microsatellite instability (MSI-H) status in gastric cancer is a favorable prognostic factor but poor data are available on its predictive role for perioperative FLOT chemotherapy in resectable gastric cancer. Here, we presented the case of two patients with advanced MSI-H gastric cancer/EGJ adenocarcinoma who had no residual tumor following neoadjuvant FLOT chemotherapy maintaining a complete response for more than 30 months, suggesting MSI-H status to be a positive prognostic marker also in patients treated with a taxane-containing triplet in this setting. We also discuss the future perspectives including the opportunity to achieve excellent clinical outcomes with immune checkpoint inhibitor (ICI)-based regimens.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905674","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":"Targeting MCM2 activates cancer-associated fibroblasts-like phenotype and affects chemo-resistance of liposarcoma cells against doxorubicin.","authors":"Chujie Bai, Shu Li, Zhichao Tan, Zhengfu Fan","doi":"10.1097/CAD.0000000000001641","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001641","url":null,"abstract":"<p><p>Liposarcoma is one of the most common soft tissue malignancies. We previously discovered upregulation of minichromosome maintenance 2 (MCM2) expression in liposarcoma tissues. Hereon, we attempt to clarify the biological influence and mechanisms of MCM2 in liposarcoma. The mRNA level of MCM2 expression was detected through the use of quantitative real-time PCR. Immunohistochemistry staining and western blot were employed to detect protein expression of MCM2. The protein expression of fibroblast-activation protein and α-smooth muscle actin was examined by immunofluorescence. Protein concentrations of interleukin (IL)-6, transforming growth factor β, and IL-8 were measured via ELISA. Furthermore, liposarcoma cell viability was assessed through cell counting kit-8 assay, and liposarcoma cell invasiveness and migration were evaluated through transwell assay. For assessing proliferation and apoptosis of liposarcoma cells, colony formation assay and flow cytometry were used. For constructing a mouse tumor model, SW872 cells were introduced into mouse flank via subcutaneous injection. MCM2 expression was boosted in liposarcoma tissues and cells when compared with the controls. MCM2-activated cancer-associated fibroblasts (CAFs)-like phenotype, presenting as increased fibroblast-activation protein expression, α-smooth muscle actin expression, cell migration, IL-6 concentration, IL-8 concentration, and transforming growth factor β concentration. Functional experiments indicated that MCM2-activated-CAFs facilitated proliferation, migration, and invasion of liposarcoma cells. Additionally, 1 μM doxorubicin treatment could not affect proliferation and apoptosis of liposarcoma cells, whereas combined use of MCM2 knockdown and 1 μM doxorubicin evidently repressed cell proliferation and promoted apoptosis. In vivo, silencing of MCM2 impaired tumor growth in mice. MCM2 overexpression promoted CAFs formation and tumor progression, showing potential value in treatment of liposarcoma.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896583","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":"Integrated single-cell and bulk RNA sequencing analyses identify an immunotherapy nonresponse-related fibroblast signature in gastric cancer.","authors":"Qian Peng, Peiling Zhang, Guolong Liu, Lin Lu","doi":"10.1097/CAD.0000000000001651","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001651","url":null,"abstract":"<p><p>Factors that determine nonresponse to immune checkpoint inhibitor (ICI) remain unclear. The protumor activities of cancer-associated fibroblasts (CAFs) suggest that they are potential therapeutic targets for cancer treatment. There is, however, a lack of CAF-related signature in predicting response to immunotherapy in gastric cancer (GC). Single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data of GC immunotherapy were downloaded from the Gene Expression Omnibus database. Bulk RNA-seq data were obtained from The Cancer Genome Atlas. The R package 'Seurat' was used for scRNA-seq data processing. Cellular infiltration, receptor-ligand interactions, and evolutionary trajectory analysis were further explored. Differentially expressed genes affecting overall survival were obtained using the limma package. Weighted Gene Correlation Network Analysis was used to identify key modules of immunotherapy nonresponder. Prognostic model was constructed by univariate Cox and least absolute contraction and selection operator analysis using the intersection of activated fibroblast genes (AFGs) with key module genes. The differences in clinicopathological features, immune microenvironment, immunotherapy prediction, and sensitivity to small molecule agents between the high- and low-risk groups were further investigated. Based on scRNA-seq, we finally identified 20 AFGs associations with the prognosis of GC patients. AFGs' high expression levels were correlated with both poor prognosis and tumor progression. Three genes (FRZB, SPARC, and FKBP10) were identified as immunotherapy nonresponse-related fibroblast genes and used to construct the prognostic signature. This signature is an independent significant risk factor affecting the clinical outcomes of GC patients. Remarkably, there were more CD4 memory T cells, resting mast cells, and M2 macrophages infiltrating in the high-risk group, which was characterized by higher tumor immune exclusion. Moreover, patients with higher risk scores were more prone to not respond to immunotherapy but were more sensitive to various small molecule agents, such as memantine. In conclusion, this study constructed a fibroblast-associated ICI nonresponse gene signature, which could predict the response to immunotherapy. This study potentially revealed a novel way to overcome immune resistance in GC.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896582","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":"Rhein exerts anti-multidrug resistance in acute myeloid leukemia via targeting FTO to inhibit AKT/mTOR.","authors":"Shuling Zhang, Lanxia Zhou, Jincai Yang, Jianle Lu, Lili Tao, Youfan Feng, Juan Cheng, Li Zhao","doi":"10.1097/CAD.0000000000001608","DOIUrl":"10.1097/CAD.0000000000001608","url":null,"abstract":"<p><p>Chemotherapy failure and resistance are the leading causes of mortality in patients with acute myeloid leukemia (AML). However, the role of m6A demethylase FTO and its inhibitor rhein in AML and AML drug resistance is unclear. Therefore, this study aimed to investigate the antileukemic effect of rhein on AML and explore its potential mechanisms underlying drug resistance. Bone marrow fluid was collected to assess FTO expression in AML. The Cell Counting Kit 8 reagent was used to assess cell viability. Migration assays were conducted to assess the cell migration capacity. Flow cytometry was used to determine the apoptotic effects of rhein and western blot analysis was used to detect protein expression. Online SynergyFinder software was used to calculate the drug synergy scores. The in-vivo antileukemic effect of rhein was assessed in an AML xenograft mouse model. We analyzed different types of AML bone marrow specimens to confirm that FTO is overexpressed in AML, particularly in cases of multidrug resistance. Subsequently, we conducted in-vivo and in-vitro investigations to explore the pharmacological activity and mechanism of rhein in AML and AML with multidrug resistance. The findings demonstrated that rhein effectively suppressed the proliferation and migration of AML cells in a time- and dose-dependent manner and induced apoptosis. Rhein targets FTO, inhibits the AKT/mTOR pathway, and exhibits synergistic antitumor effects when combined with azacitidine. This study elucidates the significant role of FTO and its inhibitor rhein in AML and AML with multidrug resistance, providing new insights for overcoming multidrug resistance in AML.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903979","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":"EGFR exon 18 delE709_T710insD mutated stage IV non-small cell lung cancer treated with osimertinib: a case report.","authors":"Sena Valcárcel, Noemi Villanueva, Carlos Álvarez, Emilio Esteban","doi":"10.1097/CAD.0000000000001605","DOIUrl":"10.1097/CAD.0000000000001605","url":null,"abstract":"<p><p>Mutations in tyrosine kinase domain of epidermal growth factor receptor (EGFR) are observed in approximately 15% of non-small cell lung cancer adenocarcinoma. Exon 19 deletions or exon 21 L858R mutations are predominant in frequency and show high sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Exon 18 mutations are extremely rare and the delE709_T710insD mutation accounts for only 0.16% of mutations when occurring as a sole mutation. This specific mutation in exon 18 seems to respond to certain EGFR TKIs such as afatinib. However, given the rarity of this mutation, determining the most effective TKI for its treatment remains unclear. We report a 70-year-old woman diagnosed with stage IV-A lung adenocarcinoma harboring EGFR delE709_T710insD mutation treated in first-line with Osimertinib using standard schedule and doses experiencing renal toxicity and disease progression after 9 weeks of treatment.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183475","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":"Pityriasiform drug eruption associated with venetoclax for acute myeloid leukaemia.","authors":"Timothy J Liu, Erin K McMeniman","doi":"10.1097/CAD.0000000000001606","DOIUrl":"10.1097/CAD.0000000000001606","url":null,"abstract":"<p><p>Venetoclax is a targeted antileukaemic therapy that has emerged as the primary treatment of acute myeloid leukaemia in patients of advanced age or who would otherwise be ineligible for standard chemotherapy. Despite the documented evidence of cutaneous side effects of venetoclax, few reports have clarified presenting cutaneous features beyond the descriptors 'rash' and 'pruritus'. In this report, we describe the development of a pityriasiform drug eruption following venetoclax-based induction therapy for acute myeloid leukaemia. This study provides further evidence to characterise the range of cutaneous adverse events that are associated with venetoclax-based therapy. Further studies are needed to elucidate the epidemiology and pathophysiology of venetoclax-induced cutaneous toxicities.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288076","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":"Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib.","authors":"Feng Ke, Nan Wang, Xuan Zhang, Rui Liu, Tingting Ren, Jing Ke, Jianye Yang, Haihan Yan, Jianmin Ma","doi":"10.1097/CAD.0000000000001615","DOIUrl":"10.1097/CAD.0000000000001615","url":null,"abstract":"<p><p>Chemotherapy remains the main approach conserving vision during the treatment of retinoblastoma, the most prevalent eye cancer in children. Unfortunately, the development of chemoresistance stands as the primary reason for treatment failure. Within this study, we showed that prolonged exposure to vincristine led to heightened expression of JAK1 and JAK2 in retinoblastoma cells, while the other members of the JAK family exhibited no such changes. Employing a genetic intervention, we demonstrated the efficacy of depleting either JAK1 or JAK2 in countering vincristine-resistant retinoblastoma cells. In addition, the dual depletion of both JAK1 and JAK2 produced a more potent inhibitory outcome compared to the depletion of either gene alone. We further demonstrated that ruxolitinib, a small molecular inhibitor of JAK1/2, effectively reduced viability and colony formation in vincristine-resistant retinoblastoma cells. It also acts synergistically with vincristine in retinoblastoma cells regardless of inherent cellular and genetic heterogeneity. The effectiveness of ruxolitinib as standalone treatment against chemoresistant retinoblastoma, as well as its combination with vincristine, was validated in multiple retinoblastoma mouse models. Importantly, mice exhibited favorable tolerance to ruxolitinib administration. We confirmed that the underlying mechanism of ruxolitinib's action in chemoresistant retinoblastoma cells is the inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. Our study reveals that the underlying mechanism driving ruxolitinib's impact on chemoresistant retinoblastoma cells is the inhibition of JAK/STAT signaling. This study reveals the contribution of JAK1/2 to the development of chemoresistance in retinoblastoma and underscores the effectiveness of targeting JAK1/2 as a strategy to sensitize retinoblastoma to chemotherapy.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921144","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":"Efficacy of nimotuzumab in combination with immunotherapy for a young recurrent cervical cancer patient: a case report and literature review.","authors":"Mingtao Shi, Yongchun Zhang","doi":"10.1097/CAD.0000000000001611","DOIUrl":"10.1097/CAD.0000000000001611","url":null,"abstract":"<p><p>Cervical cancer is one of the most common malignant tumors in women, and more than one-third of the patients have already developed to a locally advanced stage at initial diagnosis. After standard concurrent chemoradiotherapy, recurrence still occurs in 29-38% of patients with locally advanced cervical cancer (LACC), and the 5-year survival rate of patients with recurrence is only 3.8-13.0%, resulting in a poor prognosis and limited therapeutic choices. Currently, the recommended first-line systemic treatment for recurrent metastatic cervical cancer involves cisplatin or carboplatin in combination with paclitaxel-based chemotherapy, supplemented with the antivascular agent bevacizumab and the immune checkpoint inhibitor pembrolizumab. The use of these drugs, however, is limited due to side effects such as myelosuppression, gastrointestinal perforation, and bleeding, so new treatment modalities need to be explored. Anti-EGFR (epithelial growth factor receptor, anti-surface growth factor receptor antibody) targeted drugs have been demonstrated to have a significant radiosensitizing effect on synchronous chemoradiotherapy in LACC and are now considered to have potential for the treatment of recurrent cervical cancer. We represented a LACC patient who relapsed 6 months after concurrent chemoradiotherapy. The patient received six cycles of nimotuzumab combined with camrelizumab, and the efficacy was evaluated to be partial remission after two or four cycles of treatment, with progression-free survival up to 9 months, without significant side effects. Until March 2024, the patient was still undergoing treatment. Promising efficacy and tolerable side effects of nimotuzumab in combination with camrelizumab were observed in this case.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475759","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}