CancersPub Date : 2024-12-05DOI: 10.3390/cancers16234085
Arianna Di Napoli, Santo Fruscione, Sergio Mazzola, Rosalba Amodio, Giorgio Graziano, Rita Mannino, Maurizio Zarcone, Giorgio Bertolazzi, Nicole Bonaccorso, Martina Sciortino, Daniele Domenico De Bella, Alessandra Savatteri, Miriam Belluzzo, Chiara Alba Norrito, Rosario Sparacino, Paolo Contiero, Giovanna Tagliabue, Claudio Costantino, Walter Mazzucco
{"title":"Emerging Non-Breast Implant-Associated Lymphomas: A Systematic Review.","authors":"Arianna Di Napoli, Santo Fruscione, Sergio Mazzola, Rosalba Amodio, Giorgio Graziano, Rita Mannino, Maurizio Zarcone, Giorgio Bertolazzi, Nicole Bonaccorso, Martina Sciortino, Daniele Domenico De Bella, Alessandra Savatteri, Miriam Belluzzo, Chiara Alba Norrito, Rosario Sparacino, Paolo Contiero, Giovanna Tagliabue, Claudio Costantino, Walter Mazzucco","doi":"10.3390/cancers16234085","DOIUrl":"https://doi.org/10.3390/cancers16234085","url":null,"abstract":"<p><p><b>Background:</b> Medical devices used for functional or esthetic purposes improve health and quality of life; however, they are not risk-free. Anaplastic large-cell lymphoma (ALCL), associated with breast implants, is a well-known and recognized distinct lymphoma entity. More recently, additional lymphomas have been reported in relation to prosthesis other than breast implants, as these allow the pericyte to develop into a clone that undergoes a maturation process, progressing toward full malignancy. <b>Methods:</b> We performed a systematic review with a descriptive analysis of data extracted from primary studies following PRISMA guidelines, including the search string \"(IMPLANT* OR PROSTHES*) AND LYMPHOM*\" in the PubMed, Scopus, Embase, and Google-Scholar databases. Data such as patient sex, age, implant site, prosthesis material, and lymphoma type were analyzed. Statistical methods, including Student's <i>t</i>-test and Fisher's exact test, were employed to compare lymphoma characteristics, with significance set at a <i>p</i>-value < 0.05. <b>Results:</b> From a total of 5992 studies, we obtained 43 case reports and series on a total of 52 patients diagnosed with prosthesis-associated lymphomas. The majority of implant-related lymphoma cases (85%) were of the B-cell type, mostly fibrin-associated large B-cell lymphoma (LBCL). This lymphoma type was more associated with biological (non-human-derived biological tissue), metallic, and synthetic implants (synthesized from non-organic components) (<i>p</i>-value = 0.007). Patients with ALCL had equal frequencies of metal and silicone prostheses (37.5%, 3 cases each), followed by synthetic prostheses (25%, 2 cases). ALCL cases were most common at skeletal (50%) and muscular-cutaneous sites (25%), whereas B-cell lymphomas were predominantly found in cardiovascular implants (50%), followed by skeletal (27%) and muscular-cutaneous (21%) sites. Death attributed to lymphoma took place in 67% of the cases, mostly LBCL occurring in cardiovascular sites. <b>Conclusions:</b> Because the included studies were limited to case reports and series, a potential non-causal link might have been documented between different implant materials, implant sites and lymphoma types. This underscores the importance of further comprehensive research and monitoring of non-breast implants.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CancersPub Date : 2024-12-05DOI: 10.3390/cancers16234072
Francesca Consoli, Marco Tucci, Jacopo Pigozzo, Ester Simeone, Francesco Spagnolo, Teresa Troiani, Francesca Morgese, Michele Del Vecchio, Barbara Melotti, Maria Chiara Tronconi, Maria Francesca Morelli, Federica Grosso, Barbara Merelli, Ilaria Marcon, Diletta Valsecchi, Pietro Quaglino
{"title":"Retrospective-Prospective Observational Study of Italian Patients Treated in Melanoma Adjuvant Cohort MAP-MADAM (Maximing ADjuvAnt MAP): Interim Analysis.","authors":"Francesca Consoli, Marco Tucci, Jacopo Pigozzo, Ester Simeone, Francesco Spagnolo, Teresa Troiani, Francesca Morgese, Michele Del Vecchio, Barbara Melotti, Maria Chiara Tronconi, Maria Francesca Morelli, Federica Grosso, Barbara Merelli, Ilaria Marcon, Diletta Valsecchi, Pietro Quaglino","doi":"10.3390/cancers16234072","DOIUrl":"https://doi.org/10.3390/cancers16234072","url":null,"abstract":"<p><p><b>Background/Objective</b>: Dabrafenib and trametinib (D + T) have been approved for the treatment of stage III melanoma with BRAF V600E V600K mutations in an adjuvant setting, based on the results from the COMBI-AD trial. To provide early access to this combination therapy prior to its commercial availability in Italy, a Managed Access Program (MAP) was run in Italy from June 2018 to December 2019. <b>Methods</b>: The MADAM (Maximing ADjuvAnt MAP) study is an Italian retrospective-prospective observational study that included patients who received at least one dose of D + T through the MAP. The primary endpoints were relapse-free survival (RFS) and overall survival (OS). <b>Results</b>: This interim analysis presents findings after the first 24 months of follow-up. A total of 310 patients were included in the study; 240 completed the 12-month treatment with D + T, while 70 discontinued the combination. RFS rates were 93.2% at 12 months and 80.2% at 24 months. The median RFS was not reached for the overall population or any subgroups. Similarly, the median OS was not reached, with OS rates of 96.4% at 12 months and 92.5% at 24 months. <b>Conclusions</b>: D + T achieved an RFS benefit, with effects sustained beyond the treatment period, indicating positive outcomes in this patient population.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CancersPub Date : 2024-12-05DOI: 10.3390/cancers16234069
Justyna Gogola-Mruk, Izabela Kumor, Gabriela Wojtaszek, Karolina Kulig, Anna Ptak
{"title":"GW0742 as a Potential TRα and TRβ Antagonist Reduces the Viability and Metabolic Activity of an Adult Granulosa Tumour Cell Line and Simultaneously Upregulates TRβ Expression.","authors":"Justyna Gogola-Mruk, Izabela Kumor, Gabriela Wojtaszek, Karolina Kulig, Anna Ptak","doi":"10.3390/cancers16234069","DOIUrl":"https://doi.org/10.3390/cancers16234069","url":null,"abstract":"<p><strong>Background/objectives: </strong>Clinical studies have demonstrated a correlation between alterations in the expression level of TRα and TRβ receptors in ovarian cancer cells and overall survival. Celecoxib and GW0742, commonly known as a COX-2 inhibitor and a PPARβ/δ agonist, are novel thyroid hormone receptor antagonists that bind to TRβ or both TRα and TRβ.</p><p><strong>Methods: </strong>The study was conducted on a non-luteinized ovarian granulosa cell line (HGrC1) and two rare ovarian cancer cell lines (COV434 and KGN). The expression of TRα and TRβ at the gene and protein levels was examined by real-time PCR and Western blot, respectively. The impact of GW0742 and celecoxib on the cell viability of the HGrC1, COV434 and KGN lines was evaluated using the PrestoBlue™ Cell Viability Reagent. The metabolic activity of the cells was analysed using the Seahorse XFp Analyzer.</p><p><strong>Results: </strong>Initially, we observed that the gene and protein expression levels of TRα and TRβ were higher in COV434 and KGN cells than in HGrC1 cells. Subsequently, it was demonstrated that T<sub>3</sub> enhances the viability of HGrC1, COV434 and KGN cells. Furthermore, autoregulatory feedback loops were not observed during TRα or TRβ signalling in ovarian cancer cells, in contrast to the findings in healthy granulosa cells. Finally, we demonstrated that GW0742 reduced the viability and metabolic activity of granulosa cell tumours (GCTs). Simultaneously, we observed that GW0742 upregulated the expression of TRβ in GCT.</p><p><strong>Conclusions: </strong>These findings suggest that GW0742 may be a novel adjuvant therapy for GCTs expressing TRα and TRβ.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CancersPub Date : 2024-12-05DOI: 10.3390/cancers16234076
Chloe Redoute-Timonnier, Patrick Auguste
{"title":"Implication of the Extracellular Matrix in Metastatic Tumor Cell Dormancy.","authors":"Chloe Redoute-Timonnier, Patrick Auguste","doi":"10.3390/cancers16234076","DOIUrl":"https://doi.org/10.3390/cancers16234076","url":null,"abstract":"<p><p>Metastasis is the main cause of cancer-related deaths. The formation and growth of metastasis is a multistep process. Tumor cells extravasating in the secondary organ are in contact with a new microenvironment and a new extracellular matrix (ECM), called the metastatic niche. Some components of the ECM, such as periostin, can induce tumor cell growth in macrometastasis. In contrast, other components, such as Thrombospondin 1 (TSP-1), can maintain isolated cells in a dormant state. During dormancy, intracellular signaling activation, such as p38, maintains tumor cells arrested in the cell-cycle G0 phase for years. At any moment, stress can induce ECM modifications and binding to their specific receptors (mainly integrins) and reactivate dormant tumor cell growth in macrometastasis. In this review, we describe the tumor microenvironment of the different niches implicated in tumor cell dormancy. The role of ECM components and their associated receptors and intracellular signaling in the reactivation of dormant tumor cells in macrometastasis will be emphasized. We also present the different methodologies and experimental approaches used to study tumor cell dormancy. Finally, we discuss the current and future treatment strategies to avoid late metastasis relapse in patients.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CancersPub Date : 2024-12-05DOI: 10.3390/cancers16234070
Mohamed N Alibrahim, Annunziata Gloghini, Antonino Carbone
{"title":"Pathobiological Features and Therapeutic Opportunities Linked to TNF Family Member Expression in Classic Hodgkin Lymphoma.","authors":"Mohamed N Alibrahim, Annunziata Gloghini, Antonino Carbone","doi":"10.3390/cancers16234070","DOIUrl":"https://doi.org/10.3390/cancers16234070","url":null,"abstract":"<p><p>The tumor necrosis factor (TNF) family, which includes 19 ligands and 29 receptors, influences cellular proliferation, differentiation, and apoptosis. The TNF family plays a crucial role in the pathogenesis of Hodgkin lymphoma (HL), particularly through its influence on the tumor microenvironment (TME). Hodgkin Reed-Sternberg (HRS) cells, the hallmark of classic HL (cHL), exhibit overexpression of TNF receptor family members such as CD30 and CD40. Given the critical roles of CD30 and CD40 in the survival and proliferation of HRS cells within the TME, targeting these TNF receptors represents a promising therapeutic strategy; therapies that target CD30 have already shown efficacy in clinical settings. The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis plays a crucial role in immune evasion by HRS cells, which express PD-L1 that interacts with PD-1 on T cells, leading to T cell exhaustion and a diminished immune response against the tumor. By blocking this interaction, checkpoint inhibitors such as nivolumab and pembrolizumab have demonstrated high response rates in patients with cHL, particularly in those who have not responded to conventional therapies. The integration of immune checkpoint inhibitors (ICIs) with standard chemotherapy regimens has improved outcomes for patients with advanced-stage cHL. By understanding how TNF signaling interacts with immune checkpoints, researchers can design more effective treatment regimens that simultaneously target multiple pathways. Combining TNF inhibitors with checkpoint blockade therapies may enhance the overall anti-tumor response by addressing both direct tumor signaling and the immune evasion mechanisms employed by tumor cells.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CancersPub Date : 2024-12-05DOI: 10.3390/cancers16234079
Kiril V Mladenov, Ralf Stücker
{"title":"Recent Developments in Surgical Treatment of Spinal Deformity in Pediatric Patients: Experience from a Single-Center Series of 42 Neurofibromatosis Type 1 Patients.","authors":"Kiril V Mladenov, Ralf Stücker","doi":"10.3390/cancers16234079","DOIUrl":"https://doi.org/10.3390/cancers16234079","url":null,"abstract":"<p><strong>Background: </strong>The management of spinal deformities in patients with NF-1 is challenging. The study aimed to assess the outcomes of the surgical treatment of spine deformities in children with neurofibromatosis type 1 with our treatment approach.</p><p><strong>Methods: </strong>A retrospective single-center study on pediatric patients with spinal deformities associated with NF-1 who received surgical treatment between 2006 and 2024.</p><p><strong>Results: </strong>The study group comprised 42 patients with a mean age at surgery of 9.8 years. Twenty-five patients (60%) were treated by means of growth-preserving techniques and 17 patients (40%) by means of definitive fusion. Preoperative halo-gravity traction was used in 14 (33%) cases. In the group treated with a growth-preserving technique, a 54.1% mean curve correction was observed at the latest follow-up, and growth of the thoracic spine was maintained at a physiological rate; however, 25 unplanned revision surgeries (mostly due to mechanical complications) were necessary. In the group treated by definitive fusion, a 66% curve correction was achieved at initial surgery, which remained unchanged at latest follow-up, and revision surgery was performed in three cases for augmentation of the fusion mass. There was one neurological complication (2%). Another patient developed a deep wound infection (2%).</p><p><strong>Conclusions: </strong>Good and sustainable surgical correction of spinal deformities can be achieved in pediatric patients with NF-1. Due to the bony dystrophic changes, surgical treatment is challenging and the complication rate is higher than in spinal deformities of other etiologies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CancersPub Date : 2024-12-04DOI: 10.3390/cancers16234059
Kamila Krupa, Marta Fudalej, Anna Cencelewicz-Lesikow, Anna Badowska-Kozakiewicz, Aleksandra Czerw, Andrzej Deptała
{"title":"Current Treatment Methods in Hepatocellular Carcinoma.","authors":"Kamila Krupa, Marta Fudalej, Anna Cencelewicz-Lesikow, Anna Badowska-Kozakiewicz, Aleksandra Czerw, Andrzej Deptała","doi":"10.3390/cancers16234059","DOIUrl":"https://doi.org/10.3390/cancers16234059","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a prevalent malignant tumour worldwide. Depending on the stage of the tumour and liver function, a variety of treatment options are indicated. Traditional radiotherapy and chemotherapy are ineffective against HCC; however, the U.S. Food and Drug Administration (FDA) has approved radiofrequency ablation (RFA), surgical resection, and transarterial chemoembolization (TACE) for advanced HCC. On the other hand, liver transplantation is recommended in the early stages of the disease. Tyrosine kinase inhibitors (TKIs) like lenvatinib and sorafenib, immunotherapy and anti-angiogenesis therapy, including pembrolizumab, bevacizumab, tremelimumab, durvalumab, camrelizumab, and atezolizumab, are other treatment options for advanced HCC. Moreover, to maximize outcomes for patients with HCC, the combination of immune checkpoint inhibitors (ICIs) along with targeted therapies or local ablative therapy is being investigated. This review elaborates on the current status of HCC treatment, outlining the most recent clinical study results and novel approaches.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CancersPub Date : 2024-12-04DOI: 10.3390/cancers16234063
Philip Heesen, Michele Di Lonardo, Olga Ciobanu-Caraus, Georg Schelling, Daniel Zwahlen, Beata Bode-Lesniewska, Christoph Glanzmann, Gabriela Studer, Bruno Fuchs
{"title":"Ultrahypofractionated Versus Normofractionated Preoperative Radiotherapy for Soft Tissue Sarcoma: A Multicenter, Prospective Real-World-Time Phase 2 Clinical Trial.","authors":"Philip Heesen, Michele Di Lonardo, Olga Ciobanu-Caraus, Georg Schelling, Daniel Zwahlen, Beata Bode-Lesniewska, Christoph Glanzmann, Gabriela Studer, Bruno Fuchs","doi":"10.3390/cancers16234063","DOIUrl":"https://doi.org/10.3390/cancers16234063","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The historically most commonly used preoperative radiotherapy regimen for soft tissue sarcomas (STSs) consists of 50 Gray (Gy) delivered in 25 fractions over 5 weeks, achieving excellent local control, but with significant challenges due to prolonged treatment duration and early side effects. Reducing therapy duration while maintaining optimal local and distant control would be highly beneficial for patients. We aimed to investigate the outcome of an ultrahypofractionated radiotherapy (uhRT) regimen which may represent a shorter and more patient-friendly alternative. <b>Methods:</b> This multi-center, open-label, phase 2 clinical trial with a clustered cohort design was conducted within the Swiss Sarcoma Network (SSN). Adult patients (aged ≥ 18 years) with STS of the extremities or superficial trunk and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 were included. Participants were assigned to either normofractionated radiotherapy (nRT) at 50 Gy in 25 fractions or uhRT at 25 Gy in 5 fractions. Data were collected prospectively in real-world-time clinical settings. The primary outcome was local recurrence-free survival (LRFS), with overall survival (OS) and wound complications as secondary outcomes. <b>Results:</b> Between March 2020 and October 2023, 138 patients were included in the study; 74 received nRT and 64 received uhRT. The median follow-up times were 2.2 years for uhRT and 3.6 years for nRT. The LRFS rates at 1 year were 97.0% for nRT and 94.8% for uhRT (<i>p</i> = 0.57). The two-year LRFS rates were 91.9% and 94.8%, respectively (<i>p</i> = 0.57). The one- and two-year OS rates were 97.1%/86.3% and 98.2%/88.8%, respectively (<i>p</i> = 0.72). The wound complication rate was comparable between the nRT (12.0%) and uhRT (12.5%) groups (<i>p</i> = 0.99). <b>Conclusions:</b> UhRT for STSs offers an effective and safe alternative to traditional nRT, with comparable early LRFS, OS and wound complication rates. Given the two-year median follow-up, which is critical for evaluating local recurrence, uhRT shows promise as a shorter and more convenient treatment regimen. UhRT may be a safe and effective alternative treatment option to traditional nRT.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CancersPub Date : 2024-12-04DOI: 10.3390/cancers16234064
Haifa Kathrin Al-Ali, Andrew T Kuykendall, Catherine E Ellis, Janardhan Sampath, Ruben Mesa
{"title":"Anemia in Myelofibrosis: A Focus on Proactive Management and the Role of Momelotinib.","authors":"Haifa Kathrin Al-Ali, Andrew T Kuykendall, Catherine E Ellis, Janardhan Sampath, Ruben Mesa","doi":"10.3390/cancers16234064","DOIUrl":"https://doi.org/10.3390/cancers16234064","url":null,"abstract":"<p><p><b>Background:</b> Anemia is a common and progressive clinical manifestation of myelofibrosis that may occur as part of the disease pathogenesis as well as due to the myelosuppressive effects of some treatments, with a substantial impact on quality of life, prognosis, and healthcare resource utilization. Despite these burdens, anemia management has traditionally been a secondary priority to spleen and symptom control, due in part to the limitations of available therapeutic approaches. With the initial regulatory approvals of momelotinib, a Janus kinase 1 (JAK1), JAK2, and activin A receptor type 1 inhibitor that provides anemia-related benefits in addition to addressing splenomegaly and symptoms, re-evaluation of anemia as an early and prominent treatment consideration is warranted. <b>Methods:</b> In this review, we discuss the journey of patients with myelofibrosis and anemia across various severities and clinical scenarios. <b>Results:</b> Summarized are traditional approaches to anemia management and the clinical trial efficacy and safety data that support momelotinib as an option in each setting from mild to severe anemia, including in the context of co-occurring thrombocytopenia. <b>Conclusions:</b> With the availability of momelotinib and other emerging therapies directed at anemia control, early treatment of anemia to avoid progression and support improvement in eligible patients with myelofibrosis should be a primary consideration.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CancersPub Date : 2024-12-04DOI: 10.3390/cancers16234061
Fabiano Flauto, Maria Cristina De Martino, Chiara Vitiello, Rosario Pivonello, Annamaria Colao, Vincenzo Damiano
{"title":"A Review on Mitotane: A Target Therapy in Adrenocortical Carcinoma.","authors":"Fabiano Flauto, Maria Cristina De Martino, Chiara Vitiello, Rosario Pivonello, Annamaria Colao, Vincenzo Damiano","doi":"10.3390/cancers16234061","DOIUrl":"https://doi.org/10.3390/cancers16234061","url":null,"abstract":"<p><p>Adrenocortical carcinomas (ACCs) are rare and aggressive malignancies of adrenal cortex, associated with largely unknown mechanisms of biological development and poor prognosis. Currently, mitotane is the sole approved drug for treating advanced adrenocortical carcinomas (ACCs) and is being utilized more frequently as postoperative adjuvant therapy. Although it is understood that mitotane targets the adrenal cortex and disrupts steroid production, its precise mechanism of action requires further exploration. Additionally, mitotane affects cytochrome P450 enzymes, causes the depolarization of mitochondrial membranes, and leads to an accumulation of free cholesterol, ultimately resulting in cell death. Many patients treated with mitotane develop disease progression over time, underlying the need to understand the mechanisms of primary and acquired resistance. In this manuscript, we provide an overview on the intracellular mechanisms of action of mitotane, exploring data regarding predictive factors of response and evidence associated with the development of primary and acquired resistance mechanisms. In this discussion, mitotane is considered a real target therapy.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}