Cancer Biotherapy and Radiopharmaceuticals最新文献

{"title":"Immune Response to Molecular Radiotherapy with ¹⁷⁷Lu-DOTATOC: Predictive Value of Blood Cell Counts for Therapy Outcome.","authors":"Andreas Kluge, Richard P Baum, Norman Bitterlich, Harshad R Kulkarni, Ulrike Schorr-Neufing, Cees J A van Echteld","doi":"10.1089/cbr.2024.0031","DOIUrl":"10.1089/cbr.2024.0031","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> In a prior, retrospective study, 76% of patients with advanced neuroendocrine tumors undergoing ¹⁷⁷Lu-DOTATOC molecular radiotherapy (MRT) showed their best response within 8 months from the first MRT cycle. In 24% of patients, latency was much greater up to >22 months after the first cycle, and long after near-complete decay of ¹⁷⁷Lu from the last cycle. An immune response induced by MRT seems a likely explanation. As a crude measure of immunocompetence, the authors investigated whether blood cell counts (BCCs) may have predictive value for MRT outcome with ¹⁷⁷Lu-DOTATOC. <b><i>Methods:</i></b> 56 Patients with neuroendocrine tumors (NET) were administered ¹⁷⁷Lu-DOTATOC (mean 2.1 cycles; range 1-4) with median radioactivity of 7.0 GBq/cycle at 3-month intervals. Patients' BCCs were evaluated for four responder categories: CR, PR, SD, and PD (RECIST 1.1). Furthermore, baseline BCCs were correlated with progression-free survival (PFS). Finally, BCCs of patients with (PMT⁺) and without prior medical therapy (PMT^-) were compared. <b><i>Results:</i></b> Significant differences between responder categories were found for baseline hemoglobin (Hb), erythrocytes, neutrophils, lymphocytes, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and LEHN-score, integrating lymphocyte, erythrocyte, and neutrophil counts, and Hb level, but not for leukocytes and platelets. LEHN-score yielded an almost complete separation between CR and PD groups. In analogy, PFS times showed significant correlations with baseline Hb, erythrocytes, neutrophils, lymphocytes, NLR, PLR, and LEHN-score, the LEHN-score showing the strongest correlation, but not with leukocytes and platelets. For PMT^- patients, median PFS was 34.5 months, compared with 20.8 months in PMT⁺ patients, with corresponding baseline lymphocyte (32.1 ± 9.6% vs. 24.5 ± 11.6%, <i>p</i> = 0.028) and neutrophil (54.9 ± 11.6% vs. 63.5 ± 13.7%, <i>p</i> = 0.039) counts. <b><i>Conclusion:</i></b> These findings emphasize the significance of an immune response to MRT for obtaining optimal therapy efficacy and support concepts to enhance the immune response of less immunocompetent patients before MRT. It seems advisable to avoid prior or concomitant immunosuppressant medical therapy.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437846","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":"Prediction of Prognosis and Immunotherapy Response with a Novel Natural Killer Cell Marker Genes Signature in Osteosarcoma.","authors":"Qinwen Li, Xiaoyan Huang, Youfang Zhao","doi":"10.1089/cbr.2023.0103","DOIUrl":"10.1089/cbr.2023.0103","url":null,"abstract":"<p><p><b><i>Background:</i></b> Natural killer (NK) cells are characterized by their antitumor efficacy without previous sensitization, which have attracted attention in tumor immunotherapy. The heterogeneity of osteosarcoma (OS) has hindered therapeutic application of NK cell-based immunotherapy. The authors aimed to construct a novel NK cell-based signature to identify certain OS patients more responsive to immunotherapy. <b><i>Materials and Methods:</i></b> A total of eight publicly available datasets derived from patients with OS were enrolled in this study. Single-cell RNA sequencing data obtained from the Gene Expression Omnibus (GEO) database were analyzed to screen NK cell marker genes. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was used to construct an NK cell-based prognostic signature in the TARGET-OS dataset. The differences in immune cell infiltration, immune system-related metagenes, and immunotherapy response were evaluated among risk subgroups. Furthermore, this prognostic signature was experimentally validated by reverse transcription-quantitative real-time PCR (RT-qPCR). <b><i>Results:</i></b> With differentially expressed NK cell marker genes screened out, a five-gene NK cell-based prognostic signature was constructed. The prognostic predictive accuracy of the signature was validated through internal clinical subgroups and external GEO datasets. Low-risk OS patients contained higher abundances of infiltrated immune cells, especially CD8 T cells and naive CD4 T cells, indicating that T cell exhaustion states were present in the high-risk OS patients. As indicated from correlation analysis, immune system-related metagenes displayed a negative correlation with risk scores, suggesting the existence of immunosuppressive microenvironment in OS. In addition, based on responses to immune checkpoint inhibitor therapy in two immunotherapy datasets, the signature helped predict the response of OS patients to anti-programmed cell death protein 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) therapy. RT-qPCR results demonstrated the roughly consistent relationship of these five gene expressions with predicting outcomes. <b><i>Conclusions:</i></b> The NK cell-based signature is likely to be available for the survival prediction and the evaluation of immunotherapy response of OS patients, which may shed light on subsequent immunotherapy choices for OS patients. In addition, the authors revealed a potential link between immunosuppressive microenvironment and OS.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61566116","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":"LINC00641 Inhibits the Development of Cutaneous Squamous Cell Carcinoma By Downregulating miR-424 in A431 Cells.","authors":"Wenmin Liu, Xinxin Liu","doi":"10.1089/cbr.2020.4325","DOIUrl":"10.1089/cbr.2020.4325","url":null,"abstract":"<p><p><b><i>Background:</i></b> Cutaneous squamous cell carcinoma (CSCC) is the most deadly disease among nonmelanoma skin cancers. LINC00641 plays a role in various cancers, but its role in CSCC has not been reported so far. <b><i>Methods and Materials:</i></b> The expression of LINC00641 and miR-424 in cells was detected by RT-qPCR. CCK-8 and colony formation assay were used to detect the proliferation of cells. Western blot was used to detect the expression levels of proliferation-, invasion-, and migration-related proteins. Wound Healing and Transwell experiments detected the ability of cell invasion and migration. In animal experiments, a tumor-bearing model was established in nude mice, and tumor volume was measured and photographed. The expression levels of proliferation-, invasion-, and migration-related proteins were detected by Western blot. <b><i>Results:</i></b> The expression of LINC00641 was significantly decreased in CSCC cell lines. The overexpression of LINC00641 at the cellular level inhibited the proliferation and migration of CSCC cell line A431 by downregulating the expression of miR-424. The overexpression of LINC00641 in animals inhibited the tumor volume of nude mice by downregulating the expression of miR-424 to inhibit the expression of proliferation- and migration-related proteins. <b><i>Conclusion:</i></b> LINC00641 inhibits the development of CSCC by downregulating miR-424.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38896883","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":"Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for <i>Cancer Biotherapy and Radiopharmaceuticals</i>.","authors":"Alessandra Alessi","doi":"10.1089/cbr.2024.48216.rfs2023","DOIUrl":"https://doi.org/10.1089/cbr.2024.48216.rfs2023","url":null,"abstract":"","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301445","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":"WT1 And DNMT3A Mutations in Prognostic Significance of Acute Myeloid Leukemia: A Meta-Analysis.","authors":"Shiyue Ma, Lingjian Tang, Hui Tang, Chaoli Wu, Xue Pu, Jun Yang, Ninhong Niu","doi":"10.1089/cbr.2024.0093","DOIUrl":"https://doi.org/10.1089/cbr.2024.0093","url":null,"abstract":"<p><p><b><i>Background:</i></b> Adult acute leukemia most commonly manifests as acute myeloid leukemia (AML), a highly heterogeneous malignant tumor of the blood system. The application of genetic diagnostic technology is currently prevalent in numerous clinical sectors. According to recent research, the presence of specific gene mutations or rearrangements in leukemia cells is the primary cause of the disease. As different types of leukemia are caused by atypical mutated genes, testing for these mutations or rearrangements can help diagnose leukemia and identify the disease's molecular targets for treatment. <b><i>Methods:</i></b> Using the search fields \"WT1,\" \"DNMT3A,\" \"Acute myeloid leukemia,\" and \"survival,\" the CBM, Cochrane Library, Scopus, EMBASE, and PUBMED databases were separately reviewed. The methodology for evaluating the risk of bias developed by the Cochrane Collaboration was used in conjunction with a methodical evaluation of pertinent literature. Excluded studies with the following characteristics: (1) incomplete and repetitive publications, (2) unable to retrieve or convert data, (3) non-English or Chinese articles. <b><i>Results:</i></b> This analysis included 13 studies covering a total of 3478 subjects. The frequency of Wilms' Tumor 1 (WT1) mutations is 6.7%-35.73%, and the frequency of DNMT3A mutations is 12.06%-51.1%. The remission rate of patients with WT1 mutations was less than that of patients without WT1 mutations (OR = 0.22; 95% confidence interval [CI]: 0.14, 0.36; <i>p</i> < 0.00001; <i>I</i>² = 55%). The DNMT3A mutation has no statistical significance for the prognosis of AML (OR = 1.21; 95% CI: 0.93, 1.58; <i>p</i> = 0.16; <i>I</i>² = 80%). After removing one study, the heterogeneity of the indicator (mitigation rate) among other studies of DNMT3A mutation was dramatically reduced (OR = 0.63; 95% CI: 0.43, 0.93; <i>p</i> = 0.02; <i>I</i>² = 0%). <b><i>Conclusions:</i></b> Our meta-analysis shows that WT1 mutations hurt the remission rate of AML. Moreover, the impact of DNMT3A mutations on AML needs to be treated with caution. Gene diagnosis is critical for the prognosis and clinical management of AML.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114978","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":"A Comprehensive Analysis of LYAR in Colorectal Cancer: Prognostic Marker and Therapeutic Target.","authors":"Jia-Ying Wen, Ye-Ying Fang, Dong-Ming Li, Yu-Lu Tang, He-Qing Huang, Li-Min Liu, Jiang-Hui Zeng, Yi-Wu Dang, Yan-Fang Pan, Da-Tong Zeng, Wei-Jian Huang, Gang Chen, Hui Li","doi":"10.1089/cbr.2023.0181","DOIUrl":"https://doi.org/10.1089/cbr.2023.0181","url":null,"abstract":"<p><p><b><i>Background:</i></b> Colorectal cancer (CRC) is a major global health challenge with a need for new biomarkers and therapeutic targets. This work aimed to investigate the biological mechanisms and clinical value of Ly1 antibody reactive (LYAR) in CRC. <b><i>Methods:</i></b> We analyzed LYAR mRNA expression across multiple public databases, including genotype-tissue expression, gene expression omnibus, Oncomine, and the cancer genome atlas, alongside in-house immunohistochemical data to evaluate LYAR protein expression in CRC and non-CRC colorectal tissues. Gene set enrichment analysis (GSEA) was used to elucidate LYAR's biological functions, and its impact on the tumor immune microenvironment was assessed using CIBERSORT, ESTIMATE, and single-cell RNA sequencing techniques. In addition, LYAR's association with clinicopathological features and patient prognosis was explored, and its influence on drug sensitivity was investigated using the Connectivity Map database. <b><i>Results:</i></b> LYAR was significantly upregulated in CRC tissues compared with non-CRC colorectal counterparts, associated with altered immune cell composition and enhanced RNA processing, splicing, and cell cycle regulation. High LYAR expression correlated with poor disease-free and overall survival, underscoring its prognostic value. GSEA revealed LYAR's involvement in critical cellular processes and pathways, including DNA repair, cell cycle, and mTORC1 signaling. Correlation analysis identified genes positively and negatively associated with LYAR, leading to the discovery of temsirolimus and WYE-354, mTOR inhibitors, as potential therapeutic agents for CRC. Furthermore, LYAR expression predicted increased sensitivity to cetuximab in RAS wild-type metastatic CRC, indicating its utility as a biomarker for treatment responsiveness. <b><i>Conclusions:</i></b> LYAR's upregulation in CRC highlights its potential as a biomarker for prognosis and therapeutic targeting, offering insights into CRC pathology and suggesting new avenues for treatment optimization.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005928","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":"Development in the Study of Natural Killer Cells for Malignant Peritoneal Mesothelioma Treatment.","authors":"Yi-Tong Liu, He-Liang Wu, Yan-Dong Su, Yi Wang, Yan Li","doi":"10.1089/cbr.2024.0078","DOIUrl":"https://doi.org/10.1089/cbr.2024.0078","url":null,"abstract":"<p><p>Malignant peritoneal mesothelioma (MPeM) is a rare primary malignant tumor originating from peritoneal mesothelial cells. Insufficient specificity of the symptoms and their frequent reappearance following surgery make it challenging to diagnose, creating a need for more efficient treatment options. Natural killer cells (NK cells) are part of the innate immune system and are classified as lymphoid cells. Under the regulation of activating and inhibiting receptors, NK cells secrete various cytokines to exert cytotoxic effects and participate in antiforeign body, antiviral, and antitumor activities. This review provides a comprehensive summary of the specific alterations observed in NK cells following MPeM treatment, including changes in cell number, subpopulation distribution, active receptors, and cytotoxicity. In addition, we summarize the impact of various therapeutic interventions, such as chemotherapy, immunotherapy, and targeted therapy, on NK cell function post-MPeM treatment.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879866","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":"Exosome-Derived MicroRNA-221-3p Desensitizes Breast Cancer Cells to Adriamycin by Regulating <i>PIK3r1</i>-Mediated Glycose Metabolism.","authors":"Xiaolu Hong, Xiaoping Pan","doi":"10.1089/cbr.2023.0123","DOIUrl":"10.1089/cbr.2023.0123","url":null,"abstract":"<p><p><b><i>Background:</i></b> Cancer-derived exosomes facilitate chemoresistance by transferring RNAs, yet their role in exosomal microRNA-221-3p (miR-221-3p) regulation of adriamycin resistance in breast cancer (BC) remains unclear. <b><i>Methods:</i></b> Adriamycin-resistant BC cells were developed from MCF-7 and MDA-MB-231 cells by incremental adriamycin exposure. The miR-221-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction. Subsequently, exosomes were isolated and incubated with BC cells, and exosome-mediated adriamycin sensitivity was evaluated using Cell Counting Kit-8, colony formation, and flow cytometry assays. Sensitive cells were cocultured with miR-221-3p inhibitor-treated cells to assess adriamycin resistance. Moreover, the interaction between miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (<i>PIK3R1</i>) was validated using a dual luciferase reporter gene assay. Mimics and inhibitors were used to determine the effects of miR-221-3p on adriamycin resistance. <b><i>Results:</i></b> Elevated levels of miR-221-3p expression were observed in adriamycin-resistant BC cells and exosomes. Sensitive cells were cocultured with exosomes from resistant cells, resulting in increased half-maximal inhibitory concentration value and proliferation, and reduced adriamycin-induced apoptosis. However, the effects of coculturing sensitive cells with adriamycin-resistant cells were significantly weakened by miR-221-3p inhibitor transfection in adriamycin-resistant cells. <i>PIK3R1</i> was found to be a target of miR-221-3p, and miR-221-3p mimics enhanced adriamycin resistance in sensitive cells. miR-221-3p inhibitors increased the expression of <i>PIK3R1</i>, <i>p-AKT</i>, <i>c-Myc</i>, <i>HK2</i>, and <i>PKM2</i>, decreased <i>FOXO3</i> expression, and weakened the adriamycin resistance in resistant cells. <b><i>Conclusions:</i></b> miR-221-3p can be transferred between BC cells through exosomes. High levels of miR-221-3p were found to target <i>PIK3R1</i> and promoted adriamycin resistance in BC cells. [Figure: see text].</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289703","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":"RNA Interference Induces <i>BRCA1</i> Gene Methylation and Increases the Radiosensitivity of Breast Cancer Cells.","authors":"Yuebin Shi, Rui Huang, Yong Zhang, Qiang Feng, Xinyan Pan, Li Wang","doi":"10.1089/cbr.2021.0346","DOIUrl":"10.1089/cbr.2021.0346","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To investigate the relationship between breast cancer susceptibility gene-1 (<i>BRCA1</i>) gene methylation and the radiosensitivity of breast cancer. <b><i>Materials and Methods:</i></b> The authors studied three breast cancer cell lines: MDA-MB-435, MDA-MB-231, and MCF-7 cells. They constructed five short hairpin RNAs (shRNAs) and five small interfering RNAs to target selected promoter loci and initiate sequence-specific methylation in breast cancer cells. Pyrosequencing was used to analyze the state of DNA methylation. Quantitative real-time polymerase chain reaction was used to detect <i>BRCA1</i> mRNA expression and RNA-directed DNA methylation (RdDM)-related gene expression. Western blotting was performed to analyze BRCA1 protein expression. Colony formation assays and γ-histone H2A foci formation assays were conducted to assess the surviving fraction (SF) and double-strand break (DSB) repair ability of cells after irradiation. <b><i>Results:</i></b> The authors constructed five strains of lentivirus vectors and five plasmid vectors targeting <i>BRCA1</i> promoter region. In MDA-MB-435 cells, lentivirus-mediated RNA interference targeting Site 1 of BRCA1 increased the methylation levels of <i>BRCA1</i> and reduced <i>BRCA1</i> mRNA and protein expression. The SF and the ability to repair DNA DSBs were reduced in the combined LV-BRCA1RNAi-Site 1 infection and irradiation group. <b><i>Conclusions:</i></b> The authors' findings suggest that the shRNA suppressed the expression levels of the <i>BRCA1</i> gene and reduced the SF and DNA repair ability of cells after irradiation through RdDM. In summary, the radiosensitivity of breast cancer cells may correlate with <i>BRCA1</i> methylation. <b><i>Advances in Knowledge:</i></b> The authors first utilized a lentivirus-based shRNA-mediated specific-sequence DNA methylation of the <i>BRCA1</i> gene mediated by RdDM.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39797177","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":"Pyrotinib and Trastuzumab Plus Chemotherapy Serve as an Acceptable Neoadjuvant Regimen Exhibiting Good Efficacy and Tolerance in HER2-Positive Breast Cancer Patients.","authors":"Yibo Chen, Tianyi Zhang, Rui Zhang, Xuchen Cao","doi":"10.1089/cbr.2023.0175","DOIUrl":"10.1089/cbr.2023.0175","url":null,"abstract":"<p><p><b><i>Objective:</i></b> Pyrotinib, a new irreversible dual pan-human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase inhibitor blocking EGFR and HER2, has achieved a promising efficacy for advanced HER2-positive (HER2⁺) breast cancer. This study intended to further investigate the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2⁺ breast cancer treatment. <b><i>Methods:</i></b> Thirty-eight HER2⁺ breast cancer patients who received neoadjuvant pyrotinib and trastuzumab plus chemotherapy (docetaxel and carboplatin) were retrospectively reviewed. Clinical response by Response Evaluation Criteria in Solid Tumors (RECIST), pathological complete response (pCR), and adverse events data was retrieved. <b><i>Results:</i></b> According to the RECIST, the complete response rate was 0.0%, 10.5%, and 15.8% after second-cycle, fourth-cycle, and sixth-cycle therapy, respectively; whereas the objective response rate was 76.3%, 92.1%, and 100.0%, accordingly. The total pCR (tpCR) rate was 52.6%, the pCR rate of the breast was also 52.6%, and the pCR rate of lymph nodes was 86.8%. The tpCR rate was lower in patients with HER2 immunohistochemistry (IHC)++ and amplification by fluorescent <i>in situ</i> hybridization (FISH) than in those with HER2 IHC+++ (14.3% vs. 61.3%, <i>p</i> = 0.024), which was also lower in patients with Ki-67 expression ≥30% than in those with Ki-67 expression <30% (40.0% vs. 76.9%, <i>p</i> = 0.031). The common adverse events included diarrhea (84.2%), anemia (73.7%), nausea and vomiting (63.2%), fatigue (50.0%), hypomagnesemia (44.7%), leukopenia (42.1%), thrombocytopenia (39.5%), elevated transaminase (36.8%), and pruritus (31.6%). <b><i>Conclusions:</i></b> Pyrotinib and trastuzumab plus chemotherapy serve as an acceptable neoadjuvant regimen exhibiting good efficacy and tolerance in HER2⁺ breast cancer patients, while further large-scale validation is warranted.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289704","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}