Journal of Immunotherapy and Precision Oncology最新文献

{"title":"Therapeutic Role of Synthetic Lethality in <i>ARID1A</i>-Deficient Malignancies","authors":"Kyaw Z. Hein, Bettzy Stephen, Siqing Fu","doi":"10.36401/jipo-22-37","DOIUrl":"https://doi.org/10.36401/jipo-22-37","url":null,"abstract":"Abstract AT-rich interaction domain 1A (ARID1A), a mammalian switch/sucrose nonfermenting complex subunit, modulates several cellular processes by regulating chromatin accessibility. It is encoded by ARID1A, an immunosuppressive gene frequently disrupted in a many tumors, affecting the proliferation, migration, and invasion of cancer cells. Targeting molecular pathways and epigenetic regulation associated with ARID1A loss, such as inhibiting the PI3K/AKT pathway or modulating Wnt/β-catenin signaling, may help suppress tumor growth and progression. Developing epigenetic drugs like histone deacetylase or DNA methyltransferase inhibitors could restore normal chromatin structure and function in cells with ARID1A loss. As ARID1A deficiency correlates with enhanced tumor mutability, microsatellite instability, high tumor mutation burden, increased programmed death-ligand 1 expression, and T-lymphocyte infiltration, ARID1A-deficient cells can be a potential therapeutic target for immune checkpoint inhibitors that warrants further exploration. In this review, we discuss the role of ARID1A in carcinogenesis, its crosstalk with other signaling pathways, and strategies to make ARID1A-deficient cells a potential therapeutic target for patients with cancer.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"32 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135432274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to Build a Successful Phase I Clinical Trials Unit: Lessons Based on the MD Anderson Cancer Center Experience","authors":"Razelle Kurzrock, David Hong","doi":"10.36401/jipo-23-243","DOIUrl":"https://doi.org/10.36401/jipo-23-243","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"14 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135870424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment for Advanced Non–Small Lung Cancer (NSCLC) with Mutated <i>EGFR</i> in Low- and Middle-Income Countries (LMICs)","authors":"Andrés F. Cardona, Vaneza Ávila, Oscar Arrieta","doi":"10.36401/jipo-23-22","DOIUrl":"https://doi.org/10.36401/jipo-23-22","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"2 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135870536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained Clinical Response to Immunotherapy Followed by BET Inhibitor in a Patient with Unresectable Sinonasal NUT Carcinoma","authors":"Harriet Herbison, Sidney Davis, David Nickless, Andrew Haydon, Malaka Ameratunga","doi":"10.36401/jipo-23-19","DOIUrl":"https://doi.org/10.36401/jipo-23-19","url":null,"abstract":"ABSTRACT NUT carcinomas (NCs) are a group of rare tumors that can occur anywhere in the body and are defined by the fusion of the nuclear protein in testis (NUTM1) resulting in increased transcription of proto-oncogenes. NCs have a poor prognosis that varies according to the site of origin with an urgent need to develop new treatment strategies. Case reports on immunotherapy in pulmonary NC have been published, and bromodomain and extraterminal (BET) inhibitors have shown activity in NC in phase I/II trials. We present the case of a 27-year-old woman with an unresectable sinonasal NC who had a sustained clinical response to both immunotherapy and BET inhibitor therapy. This is the first reported case of immunotherapy in sinonasal NC, and it highlights the different responses to a range of treatments including BET inhibitor therapy. This case supports the theory that NCs arising from different primary sites have differing prognoses.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"46 8","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136232918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proton Craniospinal Irradiation with Immunotherapy in Two Patients with Leptomeningeal Disease from Melanoma","authors":"Ugur Sener, Mason Webb, William G. Breen, Bryan J. Neth, Nadia N. Laack, David Routman, Paul D. Brown, Anita Mahajan, Kelsey Frechette, Arkadiusz Z. Dudek, Svetomir N. Markovic, Matthew S. Block, Robert R. McWilliams, Anastasios Dimou, Lisa A. Kottschade, Heather N. Montane, Sani H. Kizilbash, Jian L. Campian","doi":"10.36401/jipo-23-20","DOIUrl":"https://doi.org/10.36401/jipo-23-20","url":null,"abstract":"ABSTRACT Introduction Proton craniospinal irradiation (pCSI) is a treatment option for leptomeningeal disease (LMD), which permits whole neuroaxis treatment while minimizing toxicity. Despite this, patients inevitably experience progression. Adding systemic therapy to pCSI may improve outcomes. Methods In this single-institution retrospective case series, we present the feasibility of treatment with pCSI (30Gy, 10 fractions) and an immune checkpoint inhibitor (ICI) in two sequential patients with LMD from melanoma. Results The first patient developed LMD related to BRAF V600E-mutant melanoma after prior ICI and BRAF-targeted therapy. After pCSI with concurrent nivolumab, the addition of relatlimab, and BRAF-targeted therapy, he remained alive 7 months after LMD diagnosis despite central nervous system progression. The second patient developed LMD related to BRAF-wildtype melanoma after up-front ICI. He received pCSI with concurrent ipilimumab and nivolumab, then nivolumab maintenance. Though therapy was held for ICI hepatitis, the patient remained progression-free 5 months after LMD diagnosis. Conclusion Adding an ICI to pCSI is feasible for patients with LMD and demonstrates a tolerable toxicity profile. While prospective evaluation is ultimately warranted, pCSI with ICI may confer survival benefits, even after prior ICI.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"42 3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136077793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histiocytic Sarcoma Treated with Pembrolizumab: A Case Report and Literature Review","authors":"Daniel Huff, Shannon Fortin Ensign, Margaret S. Ryan, Jeanne Palmer, Javier Munoz","doi":"10.36401/jipo-23-11","DOIUrl":"https://doi.org/10.36401/jipo-23-11","url":null,"abstract":"ABSTRACT Histiocytic sarcoma (HS) is a rare hematologic malignancy that has historically been treated with lymphoma-based regimens with a median survival of 6 months. We describe a case of a 51-year-old woman who presented with acute back pain and cord compression. She was diagnosed with HS with diffuse skeletal lesions and high expression of programmed death ligand 1 (PD-L1). She was subsequently treated with chemotherapy plus off-label use of pembrolizumab followed by allogeneic stem cell transplantation. Ultimately, patient died in the setting of progression of disease 17 months after her stem cell transplantation and 26 months after her diagnosis. This article also presents a literature review of cases of HS treated with programmed death ligand inhibition.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"224 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134974828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted and Immunotherapy Approaches in HER2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma: A New Era.","authors":"Maluki Radford,&nbsp;Hassan Abushukair,&nbsp;Stijn Hentzen,&nbsp;Ludimila Cavalcante,&nbsp;Anwaar Saeed","doi":"10.36401/JIPO-22-36","DOIUrl":"https://doi.org/10.36401/JIPO-22-36","url":null,"abstract":"<p><p><i>HER2</i>-targeted therapy with the <i>HER2</i> monoclonal antibody trastuzumab has achieved impressive outcomes in the first-line settings of patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma overexpressing <i>HER2</i>. However, considering that a substantial proportion of those patients eventually relapses, as well as the relatively limited performance of those agents in second-line settings, a deeper understanding of resistance mechanisms is needed for enhanced guidance for patients' therapeutic selection in the second-line setting and beyond. In this review, we highlight trastuzumab's (<i>HER2</i>-targeting agent) performance in patients with gastric or GEJ cancer, with insight into mechanisms of resistance. We also discuss the new integration of <i>PD-1</i> inhibitor pembrolizumab into the trastuzumab for gastric cancer frontline regimen, the latest addition of trastuzumab deruxtecan to the treatment armamentarium, and the potential of pipeline <i>HER2</i>-targeting approaches and combinations in patients with gastric or GEJ adenocarcinoma.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"6 3","pages":"150-157"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/45/83/i2590-017X-6-3-150.PMC10448730.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10465135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Stage IV Non-Small Cell Lung Cancer with Pembrolizumab in Combination with Platinum-Based Doublet Chemotherapy in Vietnam.","authors":"Khanh Toan Nguyen,&nbsp;To Ta Van","doi":"10.36401/JIPO-23-12","DOIUrl":"https://doi.org/10.36401/JIPO-23-12","url":null,"abstract":"<p><strong>Introduction: </strong>Lung cancer has been one of the most prevalent cancers worldwide in recent decades. According to the findings of the KEYNOTE-407 (2018) study on patients with stage IV squamous cell lung cancer, the combination of pembrolizumab and chemotherapy in the first-line treatment prolongs overall survival compared with chemotherapy alone. This study aimed to evaluate the efficacy and side effects of treating patients with stage IV non-small cell lung cancer with pembrolizumab in combination with platinum-based doublet chemotherapy.</p><p><strong>Methods: </strong>A retrospective multicenter study on 46 patients at four hospitals in Vietnam between June 2018 and August 2022. Patients received first-line treatment with a protocol of pembrolizumab in combination with platinum-based doublet chemotherapy (pemetrexed plus carboplatin or paclitaxel plus carboplatin). The study's primary endpoints were progression-free survival and safety. The secondary endpoint was overall survival.</p><p><strong>Results: </strong>The median progression-free survival was 11.0 months (95% CI, 7.4-14.7 months). The median overall survival was 23.1 months (95% CI, 18.4-27.8 months). The survival rate of patients after 1 and 2 years was 82.3% and 43.3%, respectively. The most common side effects were anemia and elevated liver enzymes, but they were primarily mild or moderate severity. Progression-free survival did not depend on cancer type based on histology (<i>p</i> = 0.13). The progression-free survival was independent of programmed death ligand-1 expression levels < 50% or ≥ 50% (<i>p</i> = 0.68).</p><p><strong>Conclusion: </strong>Treatment of stage IV non-small cell lung cancer without <i>EGFR</i> and <i>ALK</i> gene mutations with the immunotherapy protocol of pembrolizumab in combination with platinum-based doublet chemotherapy resulted in favorable outcomes without any new safety concerns. A larger sample size and longer follow-up in the future are necessary to yield more complete results.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"6 3","pages":"133-140"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/cd/i2590-017X-6-3-133.PMC10448733.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10482875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the Treatment for Advanced Non-Small-Cell Lung Cancer with Mutated Epidermal Growth Factor Receptor in Low-Income Countries: A Review.","authors":"Mousa Alali,&nbsp;Maher Saifo","doi":"10.36401/JIPO-22-29","DOIUrl":"https://doi.org/10.36401/JIPO-22-29","url":null,"abstract":"<p><strong>Introduction: </strong>Osimertinib is the treatment of choice for epidermal growth factor receptor (<i>EGFR</i>)-mutated advanced non-small-cell lung cancer (NSCLC). Because of its high price, many low-income countries, such as Syria, cannot provide osimertinib, which makes it difficult to choose the appropriate treatment for these patients. This study aimed to review articles that assessed tyrosine kinase inhibitors (TKIs) for advanced NSCLC and developed an appropriate treatment plan for Syrian patients.</p><p><strong>Methods: </strong>An electronic literature search was conducted of published phase II and III studies that assessed the efficacy of EGFR-TKIs for advanced NSCLC between January 2003 and May 2022.</p><p><strong>Results: </strong>Seventeen articles were reviewed. The results were similar when erlotinib or icotinib was compared with gefitinib. Progression-free survival and overall survival for afatinib and dacomitinib were longer than for gefitinib, with small significant differences. Osimertinib was the only TKI that showed efficacy against the T790M mutation, which showed an improvement over the first- and second-generation TKIs. Osimertinib as a first-line therapy is not cost-effective compared with first- and second-generation TKIs.</p><p><strong>Conclusion: </strong>Osimertinib is the preferred first-line treatment in patients with advanced <i>EGFR-</i>mutated NSCLC. First- and second-generation TKIs are still considered good options, especially in low-income countries that cannot cover the costs of osimertinib.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"6 3","pages":"140-149"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/33/i2590-017X-6-3-140.PMC10448734.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10482871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmune HLA Alleles and Neoepitope Presentation Predict Post-Allogenic Transplant Relapse.","authors":"Andrea Castro,&nbsp;Aaron M Goodman,&nbsp;Zachary Rane,&nbsp;James V Talwar,&nbsp;Garrett M Frampton,&nbsp;Gerald P Morris,&nbsp;Scott M Lippman,&nbsp;Xinlian Zhang,&nbsp;Razelle Kurzrock,&nbsp;Hannah Carter","doi":"10.36401/JIPO-22-19","DOIUrl":"https://doi.org/10.36401/JIPO-22-19","url":null,"abstract":"<p><strong>Introduction: </strong>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cure patients with high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, many patients relapse or develop debilitating graft-versus-host disease. Transplant restores T-cell reactivity against tumor cells, implicating patient human leukocyte antigen (HLA)-dependent antigen presentation via the major histocompatibility complex as a determinant of response. We sought to identify characteristics of the HLA genotype that influence response in allo-HSCT patients.</p><p><strong>Methods: </strong>We collected HLA genotype and panel-based somatic mutation profiles for 55 patients with AML and MDS and available data treated at the University of California San Diego Moores Cancer Center between May 2012 and January 2019. We evaluated characteristics of the HLA genotype relative to relapse-free time and overall survival (OS) post-allo-HSCT using univariable and multivariable regression.</p><p><strong>Results: </strong>In multivariable regression, the presence of an autoimmune allele was significantly associated with relapse-free time (hazard ratio [HR], 0.25; <i>p</i> = 0.01) and OS (HR, 0.16; <i>p</i> < 0.005). The better potential of the donor HLA type to present peptides harboring driver mutations trended toward better relapse-free survival (HR, 0.45; <i>p</i> = 0.07) and significantly correlated with longer OS (HR, 0.33; <i>p</i> = 0.01) though only a minority of cases had an HLA mismatch.</p><p><strong>Conclusion: </strong>In this single institution retrospective study of patients receiving allo-HSCT for relapsed AML/MDS, characteristics of an individual's HLA genotype (presence of an autoimmune allele and potential of the donor HLA to better present peptides representing driver mutations) were significantly associated with better outcomes. These findings suggest that HLA type may guide the optimal application of allo-HSCT and merit evaluation in larger cohorts. <b>ClinicalTrials.gov Identifier: NCT02478931</b>.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"6 3","pages":"127-132"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4a/e5/i2590-017X-6-3-127.PMC10448732.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10465134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}