Article
Biochemistry & Molecular Biology
Kasturee Jagirdar, Marie E. Portuallo, Meihan Wei, Matthew Wilhide, Jeremy A. Bravo Narula, Bailey M. Robertson, Gretchen M. Alicea, Crystal Aguh, Min Xiao, Tetiana Godok, Dylan Fingerman, Gregory Schuyler Brown, Meenhard Herlyn, Vissy M. Elad, Xinyu Guo, Eneda Toska, Daniel J. Zabransky, Bradley Wubbenhorst, Katherine L. Nathanson, Shawn Kwatra, Yogesh Goyal, Hongkai Ji, Qin Liu, Vito W. Rebecca
Summary: Patients with metastatic acral lentiginous melanoma (ALM) have poor response to approved melanoma therapies, and alterations in cyclin-dependent kinase 4 and 6 (CDK4/6) pathway genes contribute to resistance. This study reveals that hyperactivation of the MAPK signaling pathway and elevated cyclin D1 expression are mechanisms of intrinsic early/adaptive resistance to CDK4/6 inhibitors in ALM. Concurrent targeting of the MAPK pathway and CDK4/6 may represent a new approach to improve outcomes in patients with metastatic ALM.
Review
Oncology
Seungyeon Jung, Douglas B. Johnson
Summary: Acral and mucosal melanomas are rare subtypes of melanoma that differ from cutaneous melanoma in terms of biology and clinic. The prognosis associated with these subtypes is poor due to difficulties in early diagnosis, aggressive nature of the disease, and frequently occult sites of origin. The rarity of these subtypes has posed substantial barriers to better understanding their biological features and investigating new therapies.
Review
Immunology
Lili Mao, Zhonghui Qi, Li Zhang, Jun Guo, Lu Si
Summary: Acral and mucosal melanomas are rare in Caucasians but predominant in Asians, displaying aggressive phenotypes and similar genetic landscapes. Current therapies show limited benefit for these subtypes, and mechanisms contributing to disparities remain unclear. Early diagnosis and effective interventions for these melanoma subtypes are crucial.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, Research & Experimental
Jianping Gui, Zhen Guo, Di Wu
Summary: Acral melanoma is an aggressive subtype of melanoma that differs from other types in terms of its pathogenesis and immune microenvironment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Qingfeng Shang, Haizhen Du, Xiaowen Wu, Qian Guo, Fenghao Zhang, Ziqi Gong, Tao Jiao, Jun Guo, Yan Kong
Summary: In this study, it was found that circZNF609 plays a crucial role in the metastasis of acral and cutaneous melanoma through the circRNF609-FMRP-RAC1 axis. It regulates the stability of RAC1 mRNA by binding with FMRP, providing new insights into melanoma pathogenesis and potential targets for treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Ryan C. Augustin, Sarah Newman, Aofei Li, Marion Joy, Maureen Lyons, Mary P. Pham, Peter Lucas, Katelyn Smith, Cindy Sander, Brian Isett, Diwakar Davar, Yana G. Najjar, Hassane M. Zarour, John M. Kirkwood, Jason John Luke, Riyue Bao
Summary: In this study, we characterized acral melanoma (AM) and investigated its response to immune checkpoint inhibitors (ICIs). We found differential gene expression and pathway activation in a non-T cell-inflamed tumor microenvironment (TME) of AM, which may contribute to its poor response to ICIs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Lisa Elefanti, Carolina Zamuner, Paolo Del Fiore, Camilla Stagni, Stefania Pellegrini, Luigi Dall'Olmo, Alessio Fabozzi, Rebecca Senetta, Simone Ribero, Roberto Salmaso, Simone Mocellin, Franco Bassetto, Francesco Cavallin, Anna Lisa Tosi, Francesca Galuppini, Angelo Paolo Dei Tos, Chiara Menin, Rocco Cappellesso
Summary: Acral melanoma is a rare and aggressive subtype of melanoma, unrelated to UV radiation, with low mutation burden but frequent chromosomal rearrangements and gene amplifications. The most commonly mutated genes are BRAF, NRAS, and TP53, with some genetic alterations associated with histologic prognostic features.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yuxing Huang, Jing Su, Jiayong Liu, Xin Yi, Fang Zhou, Jiaran Zhang, Jiaxiang Wang, Xuan Meng, Lu Si, Congying Wu
Summary: This study revealed the role of YAP in promoting negative durotaxis in melanoma, elucidating the potential mechanism that the RhoA-myosin II pathway may underlie YAP-enhanced negative durotaxis in melanoma cells. Additionally, we found that acral melanoma patients exhibit YAP amplification and increased activity, and detected a decreasing stiffness gradient in the microenvironment which could facilitate the negative durotaxis of melanoma cells.
Article
Psychiatry
Hong Euy Kim, Hyun Jung Shim, Chaeyong Jung, Il Seon Shin, Jae-Min Kim, Sook Jung Yun
Summary: This study investigated the correlations between psychological distress, plasma cytokine levels, and gene mutations in melanoma patients. The results showed that psychological distress was significantly associated with certain cytokine levels and gene mutations. Psychiatric intervention and emotional support may change cytokine levels related to melanoma and have positive effects on prognosis and treatment.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Oncology
Yu Du, Caili Li, Lili Mao, Xiaoting Wei, Xue Bai, Zhihong Chi, Chuanliang Cui, Xinan Sheng, Bin Lian, Bixia Tang, Xuan Wang, Xieqiao Yan, Siming Li, Li Zhou, Jun Guo, Lu Si
Summary: This study found that the expression of Ki67 is associated with the progression and prognosis of acral melanoma (AM). Among 314 AM patients analyzed, those with high Ki67 expression had lower melanoma-specific survival. A predictive model incorporating Ki67 and other clinical factors was constructed to predict the prognosis of AM.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Pathology
Haider A. Mejbel, Carlos A. Torres-Cabala, Denai R. Milton, Doina Ivan, Laurence Feldmeyer, Kenjiro Namikawa, Priyadharsini Nagarajan, Michael T. Tetzlaff, Jonathan L. Curry, Merrick Ross, Wen-Jen Hwu, Victor G. Prieto, Phyu P. Aung
Summary: Acral lentiginous melanoma (ALM) is a rare type of cutaneous melanoma with poor prognosis. ALM patients showed significantly lower survival rates at every pathologic stage compared with non-ALM patients. Factors associated with poor prognosis in ALM patients include histologic type, SLN positivity, age, and the use of systemic therapy.
Article
Oncology
Qiong Shi, Lin Liu, Jianru Chen, Weigang Zhang, Weinan Guo, Xiao Wang, Huina Wang, Sen Guo, Qiao Yue, Jingjing Ma, Yu Liu, Guannan Zhu, Tao Zhao, Jianhong Zhao, Ying Liu, Tianwen Gao, Chunying Li
Summary: This study conducted genomic research on acral melanoma in Asian populations, identifying mutated genes associated with the disease and analyzing its pathogenesis and therapeutic targets. Additionally, it reconstructed the mutational processes of the samples and identified early mutational events. This study provides a foundation for the development of personalized strategies for treating acral melanoma in Asian populations.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Jee Yong Song, Young Jae Ryu, Ho Kyun Lee, Dong Hoon Lee, Yoo Duk Choi, Hyun Jeong Shim, Sook Jung Yun
Summary: This study investigated risk factors for sentinel lymph node (SLN) metastasis in Korean melanoma patients, with a focus on the degree of pigmentation. The results showed that Breslow thickness and heavy pigmentation were associated with SLN metastasis. Patients with positive SLN had a higher rate of loco-regional and/or distant recurrence. Heavy pigmentation was an independent predictor of SLN metastasis in both acral and non-acral melanoma.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Article
Multidisciplinary Sciences
Chao Zhang, Hongru Shen, Tielong Yang, Ting Li, Xinyue Liu, Jin Wang, Zhichao Liao, Junqiang Wei, Jia Lu, Haotian Liu, Lijie Xiang, Yichen Yang, Meng Yang, Duan Wang, Yang Li, Ruwei Xing, Sheng Teng, Jun Zhao, Yun Yang, Gang Zhao, Kexin Chen, Xiangchun Li, Jilong Yang
Summary: Studying the cell composition of acral melanoma at the single-cell level, the authors found that acral melanoma exhibits a severe immunosuppressive state compared to cutaneous melanoma, characterized by depletion of cytotoxic CD8+ T cells, enrichment of Treg cells, and exhaustion of CD8+ T cells with higher expression of PD1 and TIM-3.
NATURE COMMUNICATIONS
(2022)
Article
Pathology
Jue Hu, Xu Cai, Jiao-Jie Lv, Xiao-Chun Wan, Xue-Ying Zeng, Ming-Li Feng, Bo Dai, Yun-Yi Kong
Summary: PRAME expression in ALMs is not associated with clinical and histopathologic characteristics, but tends to be higher in cases with lymph node involvement.
Article
Biochemistry & Molecular Biology
Heather M. Brechbuhl, Mengyu Xie, Etana G. Kopin, Amy L. Han, Kiran Vinod-Paul, Jaime Hagen, Susan Edgerton, Philip Owens, Sharon Sams, Anthony Elias, Carol A. Sartorius, Aik-Choon Tan, Peter Kabos
Summary: The tumor microenvironment plays a crucial role in response and resistance to endocrine therapy in ER-positive breast cancer. The study found that neoadjuvant endocrine therapy alters TME composition, promoting the expansion of less favorable TASC(CDCP1) population associated with TME remodeling and increased immune infiltration supportive of tumor progression.
MOLECULAR CARCINOGENESIS
(2022)
Article
Multidisciplinary Sciences
Marco Napoli, Sarah J. Wu, Bethanie L. Gore, Hussein Abbas, Kyubum Lee, Rahul Checker, Shilpa Dhar, Kimal Rajapakshe, Aik Choon Tan, Min Gyu Lee, Cristian Coarfa, Elsa R. Flores
Summary: Distinct lung stem cells regulated by increment Np63 play a role in the development of both lung adenocarcinoma and squamous cell carcinoma through the regulation of a common landscape of enhancer-associated genes, including BCL9L.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Ahmad A. Tarhini, Sandra J. Lee, Aik-Choon Tan, Issam M. El Naqa, F. Stephen Hodi, Lisa H. Butterfield, William A. LaFramboise, Walter J. Storkus, Arivarasan D. Karunamurthy, Jose R. Conejo-Garcia, Patrick Hwu, Howard Streicher, Vernon K. Sondak, John M. Kirkwood
Summary: Melanoma of unknown primary (MUP) has a significantly better prognosis and shows evidence of significantly enhanced immune activation within the tumor microenvironment and the circulation in high-risk melanoma patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biology
Alyssa Obermayer, Li Dong, Qianqian Hu, Michael Golden, Jerald D. D. Noble, Paulo Rodriguez, Timothy J. J. Robinson, Mingxiang Teng, Aik-Choon Tan, Timothy I. I. Shaw
Summary: This paper presents a R Shiny framework called DRPPM-EASY for integrative multi-omics analysis of cancer datasets. The framework provides a user-friendly interface for exploring and integrating various omics data, reducing the need for computational experience. By analyzing transcriptomic and proteomic data, the authors identified cancer cell proliferative features associated with USP7 gene knockout and disruption of protein degradation and spliceosome. Additionally, they developed an extension called DRPPM-EASY-CCLE with preloaded cancer cell line data for sample querying and phenotype assignment.
Article
Medicine, Research & Experimental
Mariam Saad, Sandra J. Lee, Aik Choon Tan, Issam M. El Naqa, F. Stephen Hodi, Lisa H. Butterfield, William A. LaFramboise, Walter Storkus, Arivarasan D. Karunamurthy, Jose Conejo-Garcia, Patrick Hwu, Howard Streicher, Vernon K. Sondak, John M. Kirkwood, Ahmad A. Tarhini
Summary: This study found that female patients had better clinical response when receiving ipilimumab and high-dose IFN alpha as adjuvant therapy, and they showed stronger immune activation in the tumor microenvironment and circulation.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Xiang Liu, Bo Zhao, Timothy Shaw, Brooke L. Fridley, Derek R. Duckett, Aik Choon Tan, Mingxiang Teng
Summary: This study proposes a novel computational method for identifying differential SEs by considering the activities and positions of constituent enhancers. This method not only takes into account the overall activity changes, but also discovers four new classes of differential SEs with distinct enhancer structural alterations. Compared to existing methods, this approach shows improved identification of differential SEs and better discernment of cell-type-specific SE activity and functional interpretation.
NUCLEIC ACIDS RESEARCH
(2022)
Correction
Multidisciplinary Sciences
Marco Napoli, Sarah J. Wu, Bethanie L. Gore, Hussein A. Abbas, Kyubum Lee, Rahul Checker, Shilpa Dhar, Kimal Rajapakshe, Aik Choon Tan, Min Gyu Lee, Cristian Coarfa, Elsa R. Flores
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Jacqueline A. Turner, Emily L. Paton, Robert Van Gulick, Davide Stefanoni, Francesca Cendali, Julie Reisz, Richard P. Tobin, Martin McCarter, Angelo D'Alessandro, Raul M. Torres, William A. Robinson, Kasey L. Couts, Isabel R. Schlaepfer
Summary: BRAF mutations in cancer cells lead to a distinct lipid metabolism and dependence on fatty acids for energy. Patients who do not respond to BRAF-targeted therapy have different plasma lipid profiles compared to responders. Targeting lipid metabolism may be an alternative strategy to improve therapy response to BRAF-targeted therapies.
Article
Biochemistry & Molecular Biology
Samuel Coleman, Mengyu Xie, Ahmad A. Tarhini, Aik Choon Tan
Summary: Immunotherapy has made significant advancements in the treatment of melanoma, but there is still a need for predictive biomarkers to select patients for immune checkpoint inhibitors (ICIs) therapy. This study evaluated previously published predictive biomarkers based on gene expression signatures and found that biomarkers related to IFN-gamma-responsive genes, T and B cell markers, and chemokines in the tumor immune microenvironment can predict the response to ICIs. The study also showed that these biomarkers are more predictive in on-treatment samples compared to pretreatment samples in metastatic melanoma.
MOLECULAR CARCINOGENESIS
(2023)
Article
Cell Biology
Devin M. Boe, Holly J. Hulsebus, Kevin M. Najarro, Juliet E. Mullen, Hyunmin Kim, Aik Choon Tan, Rachel H. McMahan, Elizabeth J. Kovacs
Summary: As individuals age, alveolar macrophages (AMs) in the lower airways undergo various changes in phenotype and function, exhibiting characteristics of cellular senescence and reduced response to physiological stressors. These age-related alterations, potentially involving glucocorticoid-regulated genes, could interfere with AMs' responses to stressors and contribute to their dysfunction during healthy aging.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Medicine, General & Internal
Halis Kaan Akturk, Kasey L. Couts, Erin E. Baschal, Kagan E. Karakus, Robert J. Van Gulick, Jacqueline A. Turner, Laura Pyle, William A. Robinson, Aaron W. Michels
Summary: This study suggests that immune-related adverse events (irAEs) are associated with treatment response rates and increased survival after immune checkpoint inhibitor (ICI) therapy for advanced melanoma. Specific HLA-DR alleles are associated with different types of irAEs.
Review
Immunology
Raul M. Torres, Jacqueline A. Turner, Marc D'Antonio, Roberta Pelanda, Kimberly N. Kremer
Summary: This review discusses the role of the LPA-LPA(5) axis in peripheral immunological tolerance mechanisms and its disruption in chronic inflammation. LPA-LPA(5) signaling regulates effector cytotoxic CD8 T cells through two mechanisms and impairs tumor immunity and CD8 T cell killing in mouse models.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Multidisciplinary Sciences
Jacqueline A. Turner, Malia A. Fredrickson, Marc D'Antonio, Elizabeth Katsnelson, Morgan MacBeth, Robert Van Gulick, Tugs-Saikhan Chimed, Martin McCarter, Angelo D'Alessandro, William A. Robinson, Kasey L. Couts, Roberta Pelanda, Jared Klarquist, Richard P. Tobin, Raul M. Torres
Summary: Lysophosphatidic acid (LPA) increases in concentration in various cancer types and has an impact on CD8 T cell metabolism, phenotype, and effector functions. Plasma concentrations of LPA can predict the response to immunotherapy.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Min Hu, Samuel Coleman, Muhammad Zaki Hidayatullah Fadlullah, Daniel Spakowicz, Christine H. Chung, Aik Choon Tan
Summary: Patients with human papillomavirus-negative head and neck squamous cell carcinoma (HPV-negative HNSCC) have worse outcomes than HPV-positive HNSCC. In our study, we found that microbial signatures can distinguish Hypoxia/Immune phenotypes similar to gene expression signatures in molecularly classified tumor groups. Additionally, we identified three highly-correlated microbes that are crucial for immunotherapy response in immune processes. The co-abundance of these three microbes significantly affects the survival of patients in a molecularly heterogenous group.
Meeting Abstract
Oncology
Payman Ghasemi Saghand, Issam El Naqa, Aik Choon Tan, Mengyu Xie, Donghai Dai, James Lin Chen, Aakrosh Ratan, Martin McCarter, John D. Carpten, Harsh Shah, Alexandra Ikeguchi, Abhishek Tripathi, Igor Puzanov, Susanne M. Arnold, Michelle L. Churchman, Patrick Hwu, Jose Conejo-Garcia, William S. Dalton, George J. Weiner, Ahmad A. Tarhini
JOURNAL OF CLINICAL ONCOLOGY
(2022)