{"title":"Understanding the link between aspartame and cancer.","authors":"Morando Soffritti","doi":"10.1080/14737140.2024.2383675","DOIUrl":"10.1080/14737140.2024.2383675","url":null,"abstract":"<p><strong>Introduction: </strong>Aspartame, invented in 1965 by GD-Searle, is an intense artificial sweetener taste approximately 200 times as sweet as sucrose and used as an additive in more than 6,000 products. Aspartame (APM) was submitted for pre-marketing safety evaluation in early 1980. The studies, performed by GD-Searle, produced controversial results.</p><p><strong>Areas covered: </strong>Because of the great commercial diffusion of aspartame, in 1997 the Ramazzini Institute (RI) started a large experimental project on rodents to test the carcinogenic effects of aspartame following an experimental model with more sensitive characteristics, namely a large number of rat and mice, starting treatment from prenatal life, observation until spontaneous death. Overall, the project included studying 2270 rats and 852 mice. These studies have shown that aspartame is a carcinogenic agent in experimental animals, inducing a significant dose-related increased incidence of several types of malignant tumors and, among them, hematological neoplasia, and liver cancer.</p><p><strong>Expert opinion: </strong>The results of these studies on aspartame by the Ramazzini Institute opened a real front on the evaluation of artificial sweeteners and their possible health risks. Adequate long-term carcinogenicity bioassays on other diffuse artificial sweeteners such as acesulfame-k, sucralose, saccharin, including their blends, are likewise important for public health.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":" ","pages":"793-802"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Udhayvir S Grewal, Shiva J Gaddam, Muhammad S Beg, Timothy J Brown
{"title":"Targeted therapies in advanced biliary malignancies: a clinical review.","authors":"Udhayvir S Grewal, Shiva J Gaddam, Muhammad S Beg, Timothy J Brown","doi":"10.1080/14737140.2024.2387612","DOIUrl":"10.1080/14737140.2024.2387612","url":null,"abstract":"<p><strong>Introduction: </strong>Despite several therapeutic advancements, the proportion of patients with advanced biliary tract cancers (BTC) surviving 5 years from diagnosis remains dismal. The increasing recognition of targetable genetic alterations in BTCs has ushered in a new era in the treatment of these patients. Newer therapeutic agents targeting mutations such as isocitrate dehydrogenase (IDH), fibroblastic growth factor receptor (FGFR), human epidermal growth factor receptor (HER), and so on have established a new standard of care for treatment upon progression on frontline therapy in patients with disease harboring these mutations.</p><p><strong>Areas covered: </strong>The current review aims to concisely summarize progress with various targeted therapy options for BTC. We also briefly discuss future directions in clinical and translational research for the adoption of a personalized approach for the treatment of unresectable or advanced BTC.</p><p><strong>Expert opinion: </strong>Several new agents continue to emerge as feasible treatment options for patients with advanced BTC harboring targetable mutations. There is a growing need to identify mechanisms to conquer primary and acquired resistance to these agents. The identification of potential biomarkers that predict response to targeted therapy may be helpful in adopting a more tailored approach. All patients receiving treatment for advanced BTC should undergo tissue genomic profiling at diagnosis.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":" ","pages":"869-880"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluating the efficacy and safety of trebananib in treating ovarian cancer and non-ovarian cancer patients: a meta-analysis and systematic review.","authors":"Jialin Zhang, Jingyang Su, Yeyue Zhou, Jinhua Lu","doi":"10.1080/14737140.2024.2377793","DOIUrl":"10.1080/14737140.2024.2377793","url":null,"abstract":"<p><strong>Objectives: </strong>Due to its anti-angiogenic properties, trebananib is frequently employed in the treatment of cancer patients, particularly those with ovarian cancer. We conducted a meta-analysis to assess the efficacy and safety profile of trebananib in combination with other drugs for treating both ovarian and non-ovarian cancer patients.</p><p><strong>Methods: </strong>Our search encompassed PubMed, Medline, Cochrane, and Embase databases, with a focus on evaluating study quality. Data extraction was conducted from randomized controlled trials (RCTs), and RevMan 5.3 facilitated result analysis.</p><p><strong>Results: </strong>Combining trebananib with other drugs extended progression-free survival (PFS) [HR 0.81, (95%CI: 0.65, 0.99), <i>p</i> = 0.04] and overall survival (OS) [HR 0.88, (95%CI: 0.79, 1.00), <i>p</i> = 0.04] in ovarian cancer patients. Ovarian cancer patients exhibited a higher objective response rate (ORR) with trebananib compared to non-ovarian cancer cohorts. Moreover, the incorporation of trebananib into the standard treatment regimen for malignant tumors did not significantly elevate drug-related adverse events [RR 1.05, (95% CI: 1.00, 1.11), <i>p</i> = 0.05].</p><p><strong>Conclusion: </strong>Trebananib plus other drugs can improve the PFS, OS and ORR in patients with cancer, especially ovarian cancer. Our recommendation is to use trebananib plus other drugs to treat advanced cancer, and to continuously monitor and manage drug-related adverse events.</p><p><strong>Registration: </strong>PROSPERO (No. CRD42023466988).</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":" ","pages":"881-891"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The new life of ibrutinib therapy in CLL: enhancing personalized approaches.","authors":"Stefano Molica, Francesca Romana Mauro","doi":"10.1080/14737140.2024.2379921","DOIUrl":"10.1080/14737140.2024.2379921","url":null,"abstract":"","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":" ","pages":"789-792"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Elevated DKK1 expression: a promising prognostic biomarker and therapeutic target in head and neck squamous cell carcinoma.","authors":"Waseem Jerjes","doi":"10.1080/14737140.2024.2379920","DOIUrl":"10.1080/14737140.2024.2379920","url":null,"abstract":"","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":" ","pages":"917-919"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bevacizumab-containing treatment for relapsed or refractory Wilms tumor.","authors":"Sarah Al-Jilaihawi, Filippo Spreafico, Annelies Mavinkurve-Groothuis, Jarno Drost, Daniela Perotti, Christa Koenig, Jesper Brok","doi":"10.1080/14737140.2024.2381537","DOIUrl":"10.1080/14737140.2024.2381537","url":null,"abstract":"<p><strong>Introduction: </strong>Angiogenesis is critical for tumor growth and metastasis. Bevacizumab is an antiangiogenic drug used to treat various adult and childhood solid tumors. Its potential efficacy in Wilms tumor (WT) with poor prognosis is not established.</p><p><strong>Areas covered: </strong>The response to bevacizumab-containing regimens in relapsed or refractory WT was reviewed in available literature. Searches were conducted using PubMed, Scopus, and ClinicalTrials.gov databases. Eight papers were identified, published between 2007 and 2020, including six treatment regimens, predominantly vincristine, irinotecan, and bevacizumab (VIB) ± temozolomide (VITB). Among 16 evaluable patients, there were two complete responses, seven partial responses, five patients achieved stable disease (SD), and two patients had progressive disease. Objective responses (OR) were observed in 56% of all cases. OR or SD was observed in 89% (8/9) patients who received VIB/VITB. Bevacizumab was generally well tolerated. Related toxicities included hypertension, proteinuria, and delayed wound healing.</p><p><strong>Expert opinion: </strong>This review suggests potential effectiveness and good tolerability of bevacizumab in the setting of relapsed/refractory WT when used in combination with other drugs. Such combination therapies may serve as a bridging treatment option to other interventions and more personalized treatment options in the future; however, focused trials are needed to obtain additional evidence.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":" ","pages":"837-843"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genevieve S Silva, Ellen J Kim, Stefan K Barta, Jina Chung
{"title":"Immune-related adverse events associated with mogamulizumab: a comprehensive review of the literature.","authors":"Genevieve S Silva, Ellen J Kim, Stefan K Barta, Jina Chung","doi":"10.1080/14737140.2024.2379914","DOIUrl":"10.1080/14737140.2024.2379914","url":null,"abstract":"<p><strong>Introduction: </strong>Mogamulizumab is an anti-C-C chemokine receptor 4 antibody that is increasingly being used to treat T-cell malignancies such as cutaneous T-cell lymphoma, adult T-cell leukemia-lymphoma, and peripheral T-cell lymphoma. Because CCR4 is expressed on both malignant T-cells and regulatory T-cells (Tregs), mogamulizumab can be associated with increased immune-related adverse events (irAEs). While there is abundant literature on mogamulizumab-associated rash (MAR) and graft-versus-host disease (GVHD), other reported irAEs have not been collated into a single review.</p><p><strong>Areas covered: </strong>This narrative review covers irAEs associated with mogamulizumab in patients with T-cell lymphomas, focusing on events other than MAR and GVHD. We searched PubMed and Google Scholar for case reports, case series, chart reviews, and clinical trials published from inception to March 2024. Identified events include alopecia, vitiligo, arthritis, psoriasis, myocarditis, myositis/polymyositis, hepatitis, and others.</p><p><strong>Expert opinion: </strong>Mogamulizumab's ability to augment the host immune response through Treg depletion adds to its efficacy but has wide-ranging implications for autoimmunity across multiple organ systems, similar to immune checkpoint inhibitor therapy. Occurrence of irAEs may be associated with improved overall clinical response, although long-term follow-up studies are needed.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":" ","pages":"819-827"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefano Radaelli, Alessandra Merlini, Misbah Khan, Alessandro Gronchi
{"title":"Progress in histology specific treatments in soft tissue sarcoma.","authors":"Stefano Radaelli, Alessandra Merlini, Misbah Khan, Alessandro Gronchi","doi":"10.1080/14737140.2024.2384584","DOIUrl":"10.1080/14737140.2024.2384584","url":null,"abstract":"<p><strong>Introduction: </strong>Soft tissue sarcomas (STS) represent a heterogenous group of rare tumors, primarily treated with surgery. Preoperative radiotherapy is often recommended for extremity high-risk STS. Neoadjuvant chemotherapy, typically based on doxorubicin with ifosfamide, has shown efficacy in limbs and trunk wall STS. Second-line chemotherapy, commonly utilized in the metastatic setting, is mostly histology-driven. Molecular targeted agents are used across various histologies, and although the use of immunotherapy in STS is still in its early stages, there is increasing interest in exploring its potential.</p><p><strong>Areas covered: </strong>This article involved an extensive recent search on PubMed. It explored the current treatment landscape for localized and metastatic STS, focusing on the combined use of radiotherapy and chemotherapy for both extremity and retroperitoneal tumors, and with a particular emphasis on the most innovative histopathology driven therapeutic approaches. Additionally, ongoing clinical trials identified via clinicaltrials.gov are included.</p><p><strong>Expert opinion: </strong>Recently there have been advancements in the treatment of STS, largely driven by the outcomes of clinical trials. However further research is imperative to comprehend the effect of chemotherapy, targeted therapy and immunotherapy in various STS, as well as to identify biomarkers able to predict which patients are most likely to benefit from these treatments.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":" ","pages":"845-868"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pierre Peterlin, Esma Saada-Bouzid, Mor Moskovitz, Arnaud Pigneux, Junichiro Yuda, Mahipal Sinnollareddy, William R Henner, Diana Chen, Kevin J Freise, Rachel S Leibman, Abraham Avigdor, Toshio Shimizu
{"title":"First-in-human clinical trial results with ABBV-184, a first-in-class T-cell receptor/anti-CD3 bispecific protein, in adults with previously treated AML or NSCLC.","authors":"Pierre Peterlin, Esma Saada-Bouzid, Mor Moskovitz, Arnaud Pigneux, Junichiro Yuda, Mahipal Sinnollareddy, William R Henner, Diana Chen, Kevin J Freise, Rachel S Leibman, Abraham Avigdor, Toshio Shimizu","doi":"10.1080/14737140.2024.2373888","DOIUrl":"10.1080/14737140.2024.2373888","url":null,"abstract":"<p><strong>Background: </strong>ABBV-184, a novel survivin peptide-targeting T-cell receptor (TCR)/anti-CD3 bispecific protein, demonstrated preclinical T-cell activation and cytotoxicity toward HLA-A2:01-positive tumor lines. This first-in-human trial evaluated ABBV-184 monotherapy in patients with acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC).</p><p><strong>Research design and methods: </strong>This phase 1 multicenter, open-label, dose escalation trial (NCT04272203) enrolled adult patients with relapsed/refractory AML or NSCLC with an HLA-A2:01 restricted genotype. Patients received ABBV-184 at 0.07 ug/kg initially, with 2- to 3-fold dose increases. The primary objective was determining the ABBV-184 recommended phase 2 dose. Secondary objectives included safety, tolerability, pharmacokinetics, and immunogenicity assessments.</p><p><strong>Results: </strong>Fifteen patients enrolled in the dose escalation (8 AML and 7 NSCLC). ABBV-184 doses ranged from 0.07 mg/kg-0.7 µg/kg, with a half-life of approximately 13-29 hours. Transient cytokine increases were observed at all dose levels, and in patients with NSCLC, transient peripheral blood lymphocyte decreases were observed. The most frequently reported treatment-emergent adverse events (TEAEs) were anemia, diarrhea, and headache. Grade 1-2 infusion-related reaction (IRR) and cytokine release syndrome (CRS) TEAEs were reported.</p><p><strong>Conclusions: </strong>ABBV-184 was well tolerated and demonstrated preliminary evidence of CD3 engagement with transient cytokine increases and peripheral lymphocyte decreases.</p><p><strong>Clinical trial registration: </strong>NCT04272203.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":" ","pages":"893-904"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunotherapy in MMR-d/MSI-H recurrent/metastatic endometrial cancer.","authors":"Renata Pacholczak-Madej, Michele Bartoletti, Lucia Musacchio, Mirosława Püsküllüoglu, Paweł Blecharz, Domenica Lorusso","doi":"10.1080/14737140.2024.2367472","DOIUrl":"10.1080/14737140.2024.2367472","url":null,"abstract":"<p><strong>Introduction: </strong>The advent of immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the management of mismatch repair deficient (MMR-d)/microsatellite instability-high (MSI-H) endometrial cancer (EC). Initially investigated as monotherapy in phase I-II clinical trials for recurrent disease, immunotherapy demonstrated remarkable activity, yielding overall response rates (ORR) ranging from 27% to 58%. Based on these promising findings, phase III trials have explored the integration of immunotherapy into first-line treatment regimens for advanced/recurrent EC in combination with chemotherapy or other agents such as tyrosine kinase inhibitors (TKIs), resulting in improved ORR, progression-free survival, and overall survival compared to the standard chemotherapy regimen of paclitaxel and carboplatin. As a result, the incorporation of ICIs with standard platinum-based chemotherapy is becoming a new standard of care in MMR-d/MSI-H EC.</p><p><strong>Areas covered: </strong>This review synthesizes literature from PubMed, Embase databases, and recent congress abstracts on gynecological cancers. It covers MMR-d/MSI-H EC incidence, molecular diagnostics, clinical trial outcomes, predictive biomarkers for ICIs, patient profiles likely to benefit, resistance mechanisms, and the future of immunotherapy in this setting.</p><p><strong>Expert opinion: </strong>By offering a comprehensive overview, this review delineates the pivotal role of ICIs in the management of MMR-d/MSI-H EC.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":" ","pages":"717-729"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}