Melanoma Research最新文献_第10页

Real-world relapse-free survival data on adjuvant anti-PD-1 therapy for patients with newly diagnosed and recurrent stage III melanoma. 新诊断和复发的III期黑色素瘤患者的辅助抗pd -1治疗的真实无复发生存数据

IF 2.2 4区医学

Melanoma Research Pub Date : 2024-02-01 Epub Date: 2023-11-28 DOI: 10.1097/CMR.0000000000000946

Emma H A Stahlie, Lisanne P Zijlker, Michel W J M Wouters, Yvonne M Schrage, Winan J van Houdt, Alexander C J van Akkooi

{"title":"Real-world relapse-free survival data on adjuvant anti-PD-1 therapy for patients with newly diagnosed and recurrent stage III melanoma.","authors":"Emma H A Stahlie, Lisanne P Zijlker, Michel W J M Wouters, Yvonne M Schrage, Winan J van Houdt, Alexander C J van Akkooi","doi":"10.1097/CMR.0000000000000946","DOIUrl":"10.1097/CMR.0000000000000946","url":null,"abstract":"We aimed to compare the relapse-free survival (RFS) in patients treated with adjuvant anti-programmed cell death-1 (anti-PD-1) therapy for a first diagnosis of stage III melanoma to patients treated after resection of the recurrences. Patients treated with adjuvant anti-PD-1 therapy after complete resection of stage III melanoma between September 2018 and January 2021, were included. Depending on when adjuvant anti-PD-1 treatment was initiated, patients were divided over 2 cohorts: for the first diagnosis (cohort A) or for a second or subsequent diagnosis (cohort B) of stage III melanoma. Clinical data and RFS were compared between cohorts. 66 patients were included: 37 in cohort A, 29 in cohort B. Median follow-up time from the start of adjuvant therapy was 21 months and 17 months in cohorts A and B, respectively. Significant differences in ulceration of the primary tumor ( P = 0.032), stage according to the 7th AJCC (American Joint Committee on Cancer , P = 0.026) and type of metastatic involvement ( P = 0.005) were found between cohorts. In cohorts A and B, 18 (49%) and 8 (28%) patients developed a recurrence and the 1-year RFS was 51% and 72%, respectively. In cohort B, RFS remained longer in the patients of which the interval between first diagnosis of stage III melanoma and start of adjuvant therapy was >48 months compared to ≤48 months (83% vs. 65%, P = 0.253). This study demonstrates that patients with recurrent stage III disease, not previously treated with adjuvant systemic therapy, may derive similar benefit to a first diagnosis of stage III patients if access to adjuvant therapy changes.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"63-69"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451939","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}

引用次数: 0

Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: the non-interventional study coveNIS. cobimetinib和vemurafenib在德国现实条件下BRAF V600突变黑色素瘤伴和不伴脑转移患者中的有效性、安全性和利用率:非介入性研究coveNIS。

IF 2.2 4区医学

Melanoma Research Pub Date : 2024-02-01 Epub Date: 2023-11-13 DOI: 10.1097/CMR.0000000000000908

Katharina C Kähler, Dirk Debus, Gaston Schley, Daniela Göppner, Jessica C Hassel, Friedegund Meier, Patrick Terheyden, Rudolf Stadler, Thomas Tüting, Martin Kaatz, Norman-Philipp Hoff, Ehsan Masoudi, Agnieszka Zdanowicz-Specht, Minh Tam Nguyen, Peter Mohr

{"title":"Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: the non-interventional study coveNIS.","authors":"Katharina C Kähler, Dirk Debus, Gaston Schley, Daniela Göppner, Jessica C Hassel, Friedegund Meier, Patrick Terheyden, Rudolf Stadler, Thomas Tüting, Martin Kaatz, Norman-Philipp Hoff, Ehsan Masoudi, Agnieszka Zdanowicz-Specht, Minh Tam Nguyen, Peter Mohr","doi":"10.1097/CMR.0000000000000908","DOIUrl":"10.1097/CMR.0000000000000908","url":null,"abstract":"Cobimetinib/vemurafenib combination therapy is approved for treatment of adults with unresectable or metastatic BRAF V600 mutated malignant melanoma (mM). The non-interventional post-authorisation safety study coveNIS collected real-world data on cobimetinib/vemurafenib treatment focussing on overall survival (OS), safety and utilization. MM patients with brain metastases are usually excluded from clinical studies. coveNIS observed 2 cohorts: mM patients without (Cohort A) and with cerebral metastases (Cohort B), aiming to close the data gap for the latter population. A direct comparison of the 2 cohorts was not intended. The primary effectiveness objective was OS; the safety objective was the incidence of all and of serious adverse events (AEs). Secondary objectives included progression-free survival (PFS), time to development of cerebral metastasis (Cohort A) and time to central nervous system relapse (Cohort B). All statistical analyses were descriptive. Between 2017 and 2021, 95 patients were included (Cohort A: 54, Cohort B: 41 patients) at 32 sites in Germany. Median OS was 21.6 months in Cohort A, 7.4 months in Cohort B. Median PFS was 6.9 months in Cohort A, 5.2 months in Cohort B. The proportion of patients experiencing any AEs was 83.3% (Cohort A) and 87.8% (Cohort B). The two most common AEs in Cohort A were 'diarrhoea' (37%), 'vomiting' (20.4%) and 'pyrexia' (20.4%); in Cohort B 'diarrhoea' (36.6%) and 'fatigue' (22%). In conclusion, the OS rates in Cohort A and Cohort B of coveNIS are in line with the OS data from other trials with BRAF/MEK inhibitors for mM. No new safety signals were observed.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"44-53"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92155294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prognosis of CDKN2A germline mutation in patients with familial melanoma: a systematic review and meta-analysis. 家族性黑色素瘤患者CDKN2A种系突变的预后：一项系统综述和荟萃分析。

IF 2.2 4区医学

Melanoma Research Pub Date : 2024-02-01 Epub Date: 2023-11-02 DOI: 10.1097/CMR.0000000000000920

Ana Taibo, Sabela Paradela, Jorge Suanzes-Hernández, Vanesa Balboa-Barreiro, Javier Amado-Bouza, Eduardo Fonseca

{"title":"Prognosis of CDKN2A germline mutation in patients with familial melanoma: a systematic review and meta-analysis.","authors":"Ana Taibo, Sabela Paradela, Jorge Suanzes-Hernández, Vanesa Balboa-Barreiro, Javier Amado-Bouza, Eduardo Fonseca","doi":"10.1097/CMR.0000000000000920","DOIUrl":"10.1097/CMR.0000000000000920","url":null,"abstract":"Familial melanoma is defined as melanoma occurring in two or more first-degree relatives by the WHO. Germline mutations are isolated in a subset of them. It is well known that CDKN2A is the most frequently mutated high-risk gene in familial melanoma, however, the prognosis it confers to patients who carry its mutations is still controversial. This review aims to assess whether germline mutations imply a worse prognosis in patients with familial melanoma. A systematic review and meta-analysis were conducted by searching the electronic databases PubMed/MEDLINE, EMBASE, and Cochrane Library. Data from 3 independent populations were eventually included in the meta-analysis, involving 291 cases and 57 416 controls. The results of this systematic review and meta-analysis suggest that there is a tendency for patients with germline mutations in the CDKN2A gene to have a worse overall survival (HR = 1.30, 95% CI = 0.99-1.69, P = 0.05) and melanoma-specific survival (HR = 1.5, 95% CI = 0.97-2.31, P = 0.07). Carrier patients would not only have more incidence of melanoma and a higher risk of a second melanoma, but they also seem to have a worse prognosis. The inclusion of gene panel testing in clinical practice and the collaboration within consortia are needed to provide further evidence on the prognosis of these patients.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"9-15"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483549","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}

引用次数: 0

Intratumoural and systemic inflammation as predictors for treatment response in BRAF-mutated melanoma patients under targeted therapies. 靶向治疗下BRAF突变黑色素瘤患者的瘤内和全身炎症作为治疗反应的预测因素。

IF 2.2 4区医学

Melanoma Research Pub Date : 2024-02-01 Epub Date: 2023-11-02 DOI: 10.1097/CMR.0000000000000934

Thilo Gambichler, Maria Iordanou, Jürgen C Becker, Laura Susok

{"title":"Intratumoural and systemic inflammation as predictors for treatment response in BRAF-mutated melanoma patients under targeted therapies.","authors":"Thilo Gambichler, Maria Iordanou, Jürgen C Becker, Laura Susok","doi":"10.1097/CMR.0000000000000934","DOIUrl":"10.1097/CMR.0000000000000934","url":null,"abstract":"Intratumoural as well as systemic inflammation in melanoma has thoroughly been studied in the context of patients treated with immune checkpoint inhibitors but not with BRAF/MEK inhibitors (BRAFi/MEKi). We aimed to study whether parameters of intratumoral and systemic inflammation correlate with clinical outcome in patients with BRAF-mutant metastatic melanoma treated with BRAFi/MEKi. We studied 51 CM patients with unresectable stage III or IV who had the indication for BRAFi/MEKi treatment based on confirmed BRAF mutation. Baseline systemic immune-inflammation markers such as the systemic immune-inflammation index (SII) and the expression of intratumoral inflammation markers such as COX-2 protein expression were correlated with clinical outcome measures. On multivariable analyses, lower intratumoral COX-2 expression (OR 33.9, 95% CI 3.2-356.8) and lower SII (OR 6.3, 95% CI 1.1-34.8) proved to be significant independent predictors for objective response to targeted therapy. Elevated S100B (HR 1.2, 95% CI 1.03-1.3) was a significant predictor for progressive disease. Moreover, elevated S100B (HR 1.37, 95% CI 1.14-1.65) and LDH (HR 1.002, 95% CI 1.0001-1.003) were significant independent predictors for melanoma-specific death. In conclusion, the present study indicates that low SII values and low intratumoral COX-2 protein expression are significant independent predictors for treatment response to BRAFi/MEKi.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"80-83"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483547","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}

引用次数: 0

Small-vessel vasculitis leading to severe acute kidney injury after ipilimumab: a case report. 伊匹单抗后小血管炎导致严重急性肾损伤:1例报告。

IF 2.2 4区医学

Melanoma Research Pub Date : 2024-02-01 Epub Date: 2023-11-28 DOI: 10.1097/CMR.0000000000000928

Rui Duarte, Filipa Trigo, Ivan Luz, Paulo Santos

引用次数: 0

Underreporting of acral lentiginous melanoma in studies informing American Joint Committee on Cancer Staging System Guidelines: a review of 150 cited studies. 美国癌症分期联合委员会分期系统指南研究中对尖状皮样黑色素瘤的报告不足：对 150 项引用研究的回顾。

IF 2.2 4区医学

Melanoma Research Pub Date : 2024-02-01 Epub Date: 2023-12-19 DOI: 10.1097/CMR.0000000000000941

Katie Roster, Christopher Thang, Sumaiya Islam, Shari R Lipner

引用次数: 0

Tumour regression predicts better response to interferon therapy in melanoma patients: a retrospective single centre study. 肿瘤消退预测黑色素瘤患者对干扰素治疗的更好反应:一项回顾性单中心研究。

IF 2.2 4区医学

Melanoma Research Pub Date : 2024-02-01 Epub Date: 2023-11-13 DOI: 10.1097/CMR.0000000000000935

Noémi E Mezőlaki, Eszter Baltás, Henriette L Ócsai, Anita Varga, Irma Korom, Erika Varga, István B Németh, Erika G Kis, János Varga, Ádám Kocsis, Rolland Gyulai, Mátyás Bukva, Lajos Kemény, Judit Oláh

{"title":"Tumour regression predicts better response to interferon therapy in melanoma patients: a retrospective single centre study.","authors":"Noémi E Mezőlaki, Eszter Baltás, Henriette L Ócsai, Anita Varga, Irma Korom, Erika Varga, István B Németh, Erika G Kis, János Varga, Ádám Kocsis, Rolland Gyulai, Mátyás Bukva, Lajos Kemény, Judit Oláh","doi":"10.1097/CMR.0000000000000935","DOIUrl":"10.1097/CMR.0000000000000935","url":null,"abstract":"We hypothesise that regression may have an impact on the effectiveness of adjuvant IFN therapy, based on its role in the host immune response. Our purpose is to investigate regression and ulceration as prognostic factors in case of interferon-alpha (IFN)-treated melanoma patients. We followed 357 IFN-treated melanoma patients retrospectively, investigating progression-free survival (PFS) and overall survival (OS) depending on the presence of ulceration and regression. A Kaplan-Meier analysis was performed, and we used a Cox regression analysis to relate risk factors. The survival function of the Cox regression was used to measure the effect of regression and ulceration on PFS and OS depending on the Breslow thickness (T1-T4) of the primary tumour. Regression was significantly positively related to PFS ( P = 0.0018, HR = 0.352) and OS ( P = 0.0112, HR = 0.380), while ulceration showed a negative effect (PFS: P = 0.0001, HR = 2.629; OS: P = 0.0003, HR = 2.388). They influence survival independently. The most favourable outcome was measured in the regressed/non-ulcerated group, whereas the worse was in the non-regressed/ulcerated one. Of risk factors, Breslow thickness is the most significant predictor. The efficacy of regression is regardless of Breslow thickness, though the more favourable the impact of regression was in the thicker primary lesions. Our results indicate that regression is associated with a more favourable outcome for IFN-treated melanoma patients, whereas ulceration shows an inverse relation. Further studies are needed to analyse the survival benefit of regression in relation to innovative immune checkpoint inhibitors.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"54-62"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92155295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Mechanisms in the Etiology of Polycystic Ovary Syndrome (PCOS): A Multifaceted Hypothesis Towards the Disease with Potential Therapeutics. 多囊卵巢综合征（PCOS）病因的分子机制：多囊卵巢综合征（PCOS）病因的分子机制：关于该疾病的多方面假说及潜在疗法。

IF 1.5 4区医学

Melanoma Research Pub Date : 2024-01-01 Epub Date: 2023-03-18 DOI: 10.1007/s12291-023-01130-7

Khair Ul Nisa, Najeebul Tarfeen, Shahnaz Ahmad Mir, Ajaz Ahmad Waza, Mir Bilal Ahmad, Bashir Ahmad Ganai

{"title":"Molecular Mechanisms in the Etiology of Polycystic Ovary Syndrome (PCOS): A Multifaceted Hypothesis Towards the Disease with Potential Therapeutics.","authors":"Khair Ul Nisa, Najeebul Tarfeen, Shahnaz Ahmad Mir, Ajaz Ahmad Waza, Mir Bilal Ahmad, Bashir Ahmad Ganai","doi":"10.1007/s12291-023-01130-7","DOIUrl":"10.1007/s12291-023-01130-7","url":null,"abstract":"Among the premenopausal women, Polycystic Ovary Syndrome (PCOS) is the most prevalent endocrinopathy affecting the reproductive system and metabolic rhythms leading to disrupted menstrual cycle. Being heterogeneous in nature it is characterized by complex symptomology of oligomennorhoea, excess of androgens triggering masculine phenotypic appearance and/or multiple follicular ovaries. The etiology of this complex disorder remains somewhat doubtful and the researchers hypothesize multisystem links in the pathogenesis of this disease. In this review, we attempt to present several hypotheses that tend to contribute to the etiology of PCOS. Metabolic inflexibility, aberrant pattern of gonadotropin signaling along with the evolutionary, genetic and environmental factors have been discussed. Considered a lifelong endocrinological implication, no universal treatment is available for PCOS so far however; multiple drug therapy is often advised along with simple life style intervention is mainly advised to manage its cardinal symptoms. Here we aimed to present a summarized view of pathophysiological links of PCOS with potential therapeutic strategies.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"11 1","pages":"18-36"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10784448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83629862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of artificial intelligence and convolutional neural networks in the management of melanoma: a clinical, pathological, and radiological perspective. 人工智能和卷积神经网络在黑色素瘤管理中的作用：临床、病理和放射学视角。

IF 2.2 4区医学

Melanoma Research Pub Date : 2023-12-22 DOI: 10.1097/cmr.0000000000000951

Joshua Yee, Cliff Rosendahl, Lauren G Aoude

{"title":"The role of artificial intelligence and convolutional neural networks in the management of melanoma: a clinical, pathological, and radiological perspective.","authors":"Joshua Yee, Cliff Rosendahl, Lauren G Aoude","doi":"10.1097/cmr.0000000000000951","DOIUrl":"https://doi.org/10.1097/cmr.0000000000000951","url":null,"abstract":"Clinical dermatoscopy and pathological slide assessment are essential in the diagnosis and management of patients with cutaneous melanoma. For those presenting with stage IIC disease and beyond, radiological investigations are often considered. The dermatoscopic, whole slide and radiological images used during clinical care are often stored digitally, enabling artificial intelligence (AI) and convolutional neural networks (CNN) to learn, analyse and contribute to the clinical decision-making. To review the literature on the progression, capabilities and limitations of AI and CNN and its use in diagnosis and management of cutaneous melanoma. A keyword search of the Medline database for articles relating to cutaneous melanoma. Full-text articles were reviewed if they related to dermatoscopy, pathological slide assessment or radiology. Through analysis of 95 studies, we demonstrate that diagnostic accuracy of AI/CNN can be superior (or at least equal) to clinicians. However, variability in image acquisition, pre-processing, segmentation, and feature extraction remains challenging. With current technological abilities, AI/CNN and clinicians synergistically working together are better than one another in all subspecialty domains relating to cutaneous melanoma. AI has the potential to enhance the diagnostic capabilities of junior dermatology trainees, primary care skin cancer clinicians and general practitioners. For experienced clinicians, AI provides a cost-efficient second opinion. From a pathological and radiological perspective, CNN has the potential to improve workflow efficiency, allowing clinicians to achieve more in a finite amount of time. Until the challenges of AI/CNN are reliably met, however, they can only remain an adjunct to clinical decision-making.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"9 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139027757","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}

引用次数: 0

Combined PDE4+MEK inhibition shows antiproliferative effects in NRASQ61 mutated melanoma preclinical models. PDE4+MEK联合抑制剂在NRASQ61突变黑色素瘤临床前模型中显示出抗增殖作用。

IF 2.2 4区医学

Melanoma Research Pub Date : 2023-12-22 DOI: 10.1097/cmr.0000000000000950

Baptiste Louveau, Coralie Reger De Moura, Fanélie Jouenne, Aurélie Sadoux, Clara Allayous, Laetitia Da Meda, Mélanie Bernard-Cacciarella, Barouyr Baroudjian, Céleste Lebbé, Samia Mourah, Nicolas Dumaz

{"title":"Combined PDE4+MEK inhibition shows antiproliferative effects in NRASQ61 mutated melanoma preclinical models.","authors":"Baptiste Louveau, Coralie Reger De Moura, Fanélie Jouenne, Aurélie Sadoux, Clara Allayous, Laetitia Da Meda, Mélanie Bernard-Cacciarella, Barouyr Baroudjian, Céleste Lebbé, Samia Mourah, Nicolas Dumaz","doi":"10.1097/cmr.0000000000000950","DOIUrl":"https://doi.org/10.1097/cmr.0000000000000950","url":null,"abstract":"Upregulation of phosphodiesterase type 4 (PDE4) has been associated with worse prognosis in several cancers. In melanomas harboring NRAS mutations, PDE4 upregulation has been shown to trigger a switch in signaling from BRAF to RAF1 which leads to mitogen-activated protein kinase pathway activation. Previous in vitro evidence showed that PDE4 inhibition induced death in NRASQ61mut melanoma cells and such a strategy may thus be a relevant therapeutic option in those cases with no molecular targeted therapies approved to date. In this study, we generated patient-derived xenografts (PDX) from two NRASQ61mut melanoma lesions. We performed ex vivo histoculture drug response assays and in vivo experiments. A significant ex vivo inhibition of proliferation with the combination of roflumilast+cobimetinib was observed compared to dimethyl sulfoxyde control in both models (51 and 67%). This antiproliferative effect was confirmed in vivo for PDX-1 with a 56% inhibition of tumor growth. To decipher molecular mechanisms underlying this effect, we performed transcriptomic analyses and revealed a decrease in MKI67, RAF1 and CCND1 expression under bitherapy. Our findings strengthen the therapeutic interest of PDE4 inhibitors and support further experiments to evaluate this approach in metastatic melanoma.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"4 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139027713","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}

引用次数: 0