Pigment Cell & Melanoma Research最新文献

{"title":"Progress in melanoma treatment: Patient's perspectives","authors":"Gretchen M. Alicea,&nbsp;Jessie Villanueva,&nbsp;Marie R. Webster,&nbsp;Vito W. Rebecca","doi":"10.1111/pcmr.13138","DOIUrl":"10.1111/pcmr.13138","url":null,"abstract":"<p>Upon the 20th Anniversary of the Society for Melanoma Research, we highlight the perspectives of patients aiming to help improve future experiences, outcomes, and their quality of life over the next 20 years. Five melanoma patients generously shared their inspiring and enlightening stories of diagnosis, treatment, and outcomes. Many patients had excellent medical teams that synergistically worked together to provide an accurate diagnosis, effective treatment options, and supportive care. However, it is clear that health inequities persist in communities where people of color are predominant, affecting early detection, patient experience, and outcomes. These stories shed light on the unique challenges faced by patients and how the lack of melanoma awareness and adequate resources, especially in communities of color or low socioeconomic status, can contribute to disparate outcomes in melanoma care. We expect that these stories will raise awareness about the progress in melanoma treatment but also the existent disparities in melanoma diagnosis and treatment and the importance of early detection and prevention.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"36 6","pages":"594-601"},"PeriodicalIF":4.3,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41186667","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":"Proceedings from the Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA)","authors":"Alexander Z. Wei,&nbsp;Lanyi N. Chen,&nbsp;Marlana Orloff,&nbsp;Charlotte E. Ariyan,&nbsp;Maryam Asgari,&nbsp;Christopher A. Barker,&nbsp;Elizabeth Buchbinder,&nbsp;Sunandana Chandra,&nbsp;Kasey Couts,&nbsp;Michael M. Frumovitz,&nbsp;Andrew Futreal,&nbsp;Jeffrey E. Gershenwald,&nbsp;Ehab Y. Hanna,&nbsp;Benjamin Izar,&nbsp;Amy K. LeBlanc,&nbsp;Mario M. Leitao Jr.,&nbsp;Evan J. Lipson,&nbsp;David Liu,&nbsp;Martin McCarter,&nbsp;Jennifer L. McQuade,&nbsp;Yana Najjar,&nbsp;Suthee Rapisuwon,&nbsp;Sara Selig,&nbsp;Alexander N. Shoushtari,&nbsp;Iwei Yeh,&nbsp;Gary K. Schwartz,&nbsp;Jun Guo,&nbsp;Sapna P. Patel,&nbsp;Richard D. Carvajal","doi":"10.1111/pcmr.13139","DOIUrl":"10.1111/pcmr.13139","url":null,"abstract":"<p>Mucosal melanoma remains a rare cancer with high mortality and a paucity of therapeutic options. This is due in significant part to its low incidence leading to limited patient access to expert care and downstream clinical/basic science data for research interrogation. Clinical challenges such as delayed and at times inaccurate diagnoses, and lack of consensus tumor staging have added to the suboptimal outcomes for these patients. Clinical trials, while promising, have been difficult to activate and accrue. While individual institutions and investigators have attempted to seek solutions to such problems, international, national, and local partnership may provide the keys to more efficient and innovative paths forward. Furthermore, a mucosal melanoma coalition would provide a potential network for patients and caregivers to seek expert opinion and advice. The Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA) highlighted the current clinical challenges faced by patients, providers, and scientists, identified current and future clinical trial investigations in this rare disease space, and aimed to increase national and international collaboration among the mucosal melanoma community in an effort to improve patient outcomes. The included proceedings highlight the clinical challenges of mucosal melanoma, global clinical trial experience, basic science advances in mucosal melanoma, and future directions, including the creation of shared rare tumor registries and enhanced collaborations.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"36 6","pages":"542-556"},"PeriodicalIF":4.3,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41110638","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":"Nrf2 protein in melanoma progression, as a new means of treatment","authors":"Qun Feng,&nbsp;Xiaolin Xu,&nbsp;Shoulin Zhang","doi":"10.1111/pcmr.13137","DOIUrl":"10.1111/pcmr.13137","url":null,"abstract":"<p>Melanoma is a potentially lethal form of skin cancer resulting from the unlimited proliferation of melanocytes. Melanocytic lineage appears to have a greater rate of reactive oxygen species (ROS) production, possibly as a result of exposure to ultraviolet (UV) light and the production of melanin. It has been established that nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a master regulator of the cellular response to oxidative stresses. Recent research has shown that the Nrf2 and its critical negative regulator Kelch-like ECH-associated protein 1 (Keap1) are misregulated in melanoma, and the Keap1-Nrf2 pathway has emerged as a promising new target for treating and preventing melanoma. In melanoma, Nrf2 may either limit tumor growth or promote its development. This review covers a wide range of topics, including the dual functions played by the Keap1-Nrf2 signaling pathway in melanoma and the most recent targeting techniques of the Nrf2.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 2","pages":"247-258"},"PeriodicalIF":4.3,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41097733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laser capture microdissection provides a novel molecular profile of human primary cutaneous melanoma","authors":"Kristina Navrazhina,&nbsp;Sandra Garcet,&nbsp;Samuel C. Williams,&nbsp;Nicholas Gulati,&nbsp;Felix Kiecker,&nbsp;John W. Frew,&nbsp;Hiroshi Mitsui,&nbsp;James G. Krueger","doi":"10.1111/pcmr.13121","DOIUrl":"10.1111/pcmr.13121","url":null,"abstract":"<p>Melanoma accounts for the majority of skin cancer-related mortality, highlighting the need to better understand melanoma initiation and progression. In-depth molecular analysis of neoplastic melanocytes in whole tissue biopsies may be diluted by inflammatory infiltration, which may obscure gene signatures specific to neoplastic cells. Thus, a method is needed to precisely uncover molecular changes specific to tumor cells from a limited sample of primary melanomas. Here, we performed laser capture microdissection (LCM) and gene expression profiling of patient-derived frozen sections of pigmented lesions and primary cutaneous melanoma. Compared to bulk tissue analysis, analysis of LCM-derived samples identified 9528 additional differentially expressed genes (DEGs) including melanocyte-specific genes like PMEL and TYR, with enriched of pathways related to cell proliferation. LCM methodology also identified potentially targetable kinases specific to melanoma cells that were not detected by bulk tissue analysis. Taken together, our data demonstrate that there are marked differences in gene expression profiles depending on the method of sample isolation. We found that LCM captured higher expression of melanoma-related genes while whole tissue biopsy identified a wider range of inflammatory markers. Taken together, our data demonstrate that LCM is a valid approach to identify melanoma-specific changes using a relatively small amount of primary patient-derived melanoma sample.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 1","pages":"81-89"},"PeriodicalIF":4.3,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41092543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A twenty year perspective on melanoma therapy","authors":"Keith T. Flaherty","doi":"10.1111/pcmr.13125","DOIUrl":"10.1111/pcmr.13125","url":null,"abstract":"<p>Melanoma had long been considered to be particularly addressable with immunotherapy, but that reputation was built on modestly effective cytokine-based immunotherapy. CTLA-4 antibody therapy reinforced this legacy, but PD-1 antibodies transformed the melanoma treatment landscape and lead the way for immunotherapy to become standard treatment for more than half of the advanced cancer population. BRAF mutations were discovered in 8% of all cancer and nearly 50% of melanomas. Successful development of BRAF inhibitors and BRAF/MEK combination therapy in melanoma preceded regulatory approval across all cancer types. No cancer type saw outcomes improved by the same margin as melanoma in the decade of the 2010s.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"36 6","pages":"563-575"},"PeriodicalIF":4.3,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41097731","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":"A meta-analysis of the placebo response in vitiligo: Causes and consequences for the interpretation of clinical trials","authors":"Reinhart Speeckaert,&nbsp;Marijn M. Speeckaert,&nbsp;Nanja van Geel","doi":"10.1111/pcmr.13132","DOIUrl":"10.1111/pcmr.13132","url":null,"abstract":"<p>The current understanding of the placebo response in vitiligo is limited. Nonetheless, it is difficult to compare the outcomes of vitiligo trials if the repigmentation rates in placebo patients vary significantly. We conducted a meta-analysis of the placebo response in vitiligo trials. Overall, repigmentation rates in patients receiving placebo were 22%, ranging substantially from 0 to 60%. Repigmentation (&gt;25%) was still relatively common for placebo (9.35%), but fell to 5% when &gt;50% improvement was analyzed. Higher frequencies of placebo responses correlated with more repigmentation in the intervention groups. Facial vitiligo and sunlight exposure was linked to higher placebo responses. Roughly estimating the amount of improvement using quartiles (0–25, 25%–50%, 50%–75%, 75%–100% repigmentation) resulted in higher placebo rates compared to other assessment methods. In clinical studies with older patients, the ratio of placebo reactions to treatment responses was higher. This is likely because clinical trials with older patients reported less repigmentation after treatment than studies with younger patients. The percentual difference in affected body surface area during the study period ranged from 6.2% worsening to 17.6% improvement in the placebo groups. This high variability in placebo responses illustrates the need for standardized outcome measures and more head-to-head trials in vitiligo.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 1","pages":"74-80"},"PeriodicalIF":4.3,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093870","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":"Anti-melanogenic effect of exosomes derived from human dermal fibroblasts (BJ-5ta-Ex) in C57BL/6 mice and B16F10 melanoma cells","authors":"Jung Min Lee,&nbsp;Jung Ok Lee,&nbsp;Yujin Kim,&nbsp;You Na Jang,&nbsp;A. Yeon Park,&nbsp;Su-Young Kim,&nbsp;Hye Sung Han,&nbsp;Beom Joon Kim,&nbsp;Kwang Ho Yoo","doi":"10.1111/pcmr.13135","DOIUrl":"10.1111/pcmr.13135","url":null,"abstract":"<p>Exosomes are involved in intercellular communication by transferring cargo between cells and altering the specific functions of the target cells. Recent studies have demonstrated the therapeutic effects of exosomes in several skin diseases. However, understanding of the effects of exosomes on anti-pigmentation is limited. Therefore, we investigated whether BJ-5ta exosomes (BJ-5ta-Ex) derived from human foreskin fibroblasts regulate melanogenesis and delineated the underlying mechanism. Interestingly, treatment with BJ-5ta-Ex induced decreased melanin content, tyrosinase (TYR) activity, and expression of melanogenesis-related genes, including microphthalmia-related transcription factor (MITF), TYR, tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2). In addition, BJ-5ta-Ex downregulated the cAMP/PKA and GSK-3β/β-catenin signaling pathways and upregulated the MAPK/ERK signaling pathway. Notably, treatment with BJ-5ta-Ex inhibited α-melanocyte-stimulating hormone-induced melanosome transport and decreased the expression of key proteins involved in melanosome transport, namely, rab27a and melanophilin (MLPH). To further confirm the depigmenting effects of BJ-5ta-Ex, we conducted experiments using a three-dimensional reconstituted human full skin model and ultraviolet B (UVB)-irradiated mouse model. Treatment with BJ-5ta-Ex improved tissue brightness and reduced the distribution of melanosomes. In UVB-irradiated mouse ears, BJ-5ta-Ex reduced the number of active melanocytes and melanin granules. These results demonstrate that BJ-5ta-Ex can be useful for the clinical treatment of hyperpigmentation disorders.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 2","pages":"232-246"},"PeriodicalIF":4.3,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41096412","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":"Brief history of the Society for Melanoma Research: A community of clinicians, researchers, and friends","authors":"Vito W. Rebecca,&nbsp;Jessie Villanueva,&nbsp;Marie R. Webster","doi":"10.1111/pcmr.13124","DOIUrl":"10.1111/pcmr.13124","url":null,"abstract":"<p>To commemorate the 20th Anniversary of the Society of Melanoma Research and the first International Melanoma Research Congress held in June of 2003, we have described in brief, how the Society for Melanoma Research (SMR) began, the purpose, goals, and governance of the SMR, and how the society has evolved to support new melanoma researchers. In celebration of the immense progress in treating melanoma patients over the last 20 years and the impact of the SMR on these advances, we have highlighted memories and insight from early SMR members and founders.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"36 6","pages":"576-582"},"PeriodicalIF":4.3,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41097732","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":"Twenty years of research in melanoma therapy–From “nothing works” to cures: A personal account","authors":"Meenhard Herlyn,&nbsp;Jessie Villanueva","doi":"10.1111/pcmr.13133","DOIUrl":"10.1111/pcmr.13133","url":null,"abstract":"&lt;p&gt;In the late 1990s and early 2000s the mood in the melanoma field was grim. “Nothing works,” said our oncology colleague Lynn Schuchter, after the third large Phase III trial in immune therapy (a MAGE3 trial) failed. Don Morton's Bacillus Calmette-Guérin (BCG) trial had also just failed, and he was truly disappointed (Eilber et al., &lt;span&gt;1976&lt;/span&gt;; Morton et al., &lt;span&gt;1974&lt;/span&gt;). There were no alternatives, no hope. The melanoma research field was small, underfunded, and isolated. While oncologists, surgeons, pathologists, and epidemiologists continued spirited debates about their newest findings in specialized meetings, the melanoma experimental researchers were few and widely scattered. Prior to the founding of the Society for Melanoma Research (SMR), melanoma researchers did not have an intellectual home. There was no organized pipeline for attracting young researchers, there were no tissue banks, no databases, and the field lacked animal models beyond a few transplantable tumors such as the B16 model or nude mouse xenograft models. The incidence of melanoma had been rising since the 1950s at an alarming rate of 2%–5%/year. Treatment of advanced disease had not improved in the past 30+ years and the failures of the latest large clinical trials hammered down the point that melanoma ranked among those cancers with the lowest 5-year survival rates, almost on par with pancreatic cancer or glioma.&lt;/p&gt;&lt;p&gt;The field could build on progress, which demonstrated an immune response could be activated in melanoma patients. Monoclonal antibodies had helped to define ~200 melanoma-associated markers, mostly cell surface receptors used for adhesion or growth signaling. However, those monoclonal antibodies defied all attempts to use them as “magic bullets” for therapy. The first oncogene (NRAS) in melanoma was initially defined by Anthony Albino, and colleagues at MSKCC (Albino et al., &lt;span&gt;1984&lt;/span&gt;), but NRAS continues to defy any therapeutic targeting to this day. [Correction added on 19 October 2023, after first online publication: In the previous sentence, “The first oncogene (NRAS) had been” was changed to “The first oncogene (NRAS) in melanoma was initially”.]&lt;/p&gt;&lt;p&gt;In June 2002, Barbara Weber from the University of Pennsylvania called: “Tomorrow there is a &lt;i&gt;Nature&lt;/i&gt; paper from Mike Stratton's lab at the Sanger Institute, coming out on a new oncogene that will transform the field.” Andy Futreal, Michael Stratton, and colleagues had conducted a tour-de-force in sequencing cancer cell lines of different origin. A point mutation in the BRAF gene was found predominantly in melanoma (Davies et al., &lt;span&gt;2002&lt;/span&gt;). A new research era began for experimental and clinical researchers alike. Initially, the field was skeptical because the MAPK pathway is activated in nearly all melanomas regardless of the mutational profile. BRAF&lt;sup&gt;V599E&lt;/sup&gt; became BRAF&lt;sup&gt;V600E&lt;/sup&gt;, conquered the field, and captured the imagination of many cancer researc","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"36 6","pages":"583-587"},"PeriodicalIF":4.3,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41099306","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":"Unsuspected consequences of synonymous and missense variants in OCA2 can be detected in blood cell RNA samples of patients with albinism","authors":"Vincent Michaud,&nbsp;Angèle Sequeira,&nbsp;Elina Mercier,&nbsp;Eulalie Lasseaux,&nbsp;Claudio Plaisant,&nbsp;Smail Hadj-Rabia,&nbsp;Sandra Whalen,&nbsp;Dominique Bonneau,&nbsp;Anne Dieux-Coeslier,&nbsp;Fanny Morice-Picard,&nbsp;Juliette Coursimault,&nbsp;Benoît Arveiler,&nbsp;Sophie Javerzat","doi":"10.1111/pcmr.13123","DOIUrl":"10.1111/pcmr.13123","url":null,"abstract":"<p>Oculocutaneous albinism type 2 (OCA2) is the second most frequent form of albinism and represents about 30% of OCA worldwide. As with all types of OCA, patients present with hypopigmentation of hair and skin, as well as severe visual abnormalities. We focused on a subgroup of 29 patients for whom genetic diagnosis was pending because at least one of their identified variants in or around exon 10 of <i>OCA2</i> is of uncertain significance (VUS). By minigene assay, we investigated the effect of these VUS on exon 10 skipping and showed that not only intronic but also some synonymous variants can result in enhanced exon skipping. We further found that excessive skipping of exon 10 could be detected directly on blood samples of patients and of their one parent with the causal variant, avoiding invasive skin biopsies. Moreover, we show that variants, which result in lack of detectable <i>OCA2</i> mRNA can be identified from blood samples as well, as shown for the most common <i>OCA2</i> pathogenic missense variant c.1327G&gt;A/p.(Val443Ile). In conclusion, blood cell RNA analysis allows testing the potential effect of any <i>OCA2</i> VUS on transcription products. This should help to elucidate yet unsolved OCA2 patients and improve genetic counseling.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 5","pages":"534-545"},"PeriodicalIF":3.9,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}