Article
Biochemistry & Molecular Biology
Cherie-Ann Nathan, Alok R. Khandelwal, Gregory T. Wolf, Juan P. Rodrigo, Antti A. Makitie, Nabil F. Saba, Arlene A. Forastiere, Carol R. Bradford, Alfio Ferlito
Summary: This review summarizes the current evidence and impact of TP53 mutations in head and neck squamous cell carcinomas (HNSCC), including their association with tumor invasion, metastasis, genomic instability, and cell proliferation, as well as their link to increased aggressiveness and reduced survival after surgical treatment of HNSCC.
MOLECULAR CARCINOGENESIS
(2022)
Article
Oncology
Joanna Sobocinska, Joanna Nowakowska, Sara Molenda, Anna Olechnowicz, Kacper Guglas, Joanna Kozlowska-Maslon, Urszula Kazimierczak, Marta Machnik, Urszula Oleksiewicz, Anna Teresiak, Katarzyna Lamperska, Tomasz Kolenda
Summary: This study found that the expression of ZNF540 is closely associated with clinical-pathological parameters and HPV infection in head and neck squamous cell carcinoma patients. High levels of ZNF540 expression are correlated with better survival rates, suggesting its potential as a biomarker for prognosis and treatment of HNSCC.
Review
Biochemistry & Molecular Biology
Yingming Sun, Zhe Wang, Sufang Qiu, Ruoyu Wang
Summary: HNSCC, the 9th most common malignant tumor worldwide, can be divided into HPV-related and HPV-unrelated subtypes based on etiology. HPV-positive HNSCC is more sensitive to treatment with better survival rates, requiring individualized therapy. EGFR amplification and PI3K/AKT/mTOR pathway aberrant activation are common in HPV-positive HNSCC.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Oncology
Matthew Uzelac, Armon Barakchi, Varsha Beldona, Daniel John, Jaideep Chakladar, Wei Tse Li, Weg M. M. Ongkeko
Summary: This study examines genomic mutations in HPV-infected HNSCC patients and finds that high expression of E6 and E7 oncoproteins is associated with an increase in point mutations and specific chromosomal alterations.
Article
Oncology
Oliwia Koteluk, Antonina Bielicka, Zaneta Lemanska, Kacper Jozwiak, Weronika Klawiter, Andrzej Mackiewicz, Urszula Kazimierczak, Tomasz Kolenda
Summary: In this study, we identified ANO1, TMEM156, TMEM173, and TMEM213 as potential biomarkers for head and neck squamous cell carcinoma (HNSCC) based on TCGA data analysis. These TMEM genes were found to be associated with patient survival and enrichment of genes involved in various biological processes, particularly metastasis and immune response.
Article
Oncology
Sara Varatanovic, Stefan Stoiber, Markus Haas, Alexander Lein, Lorenz Kadletz-Wanke, Faris F. Brkic
Summary: MK0752 shows potential as a therapeutic agent for HPV-positive HNSCC by exhibiting antineoplastic effects and inducing apoptosis. Further investigation is needed to validate these findings and understand the underlying mechanisms.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Junwei Xiang, Yaodong He, Yunshan Li, Kexuan Wu, Mengxiang Cheng, Yuanyin Wang, Ran Chen
Summary: In this study, a risk assessment model consisting of 14 hrlncRNA pairs was constructed for predicting and guiding the prognosis and treatment of HNSCC patients. High-risk patients had unfavorable prognosis and significant differences in TMB and tumor immune infiltration compared to the low-risk group. The model has potential clinical applications.
Review
Oncology
Sharon Changshan Wu, Karl Munger
Summary: Cancer/testis antigens show potential as therapeutic targets and prognostic biomarkers in head and neck squamous cell carcinoma, warranting further study to elucidate their role in the pathogenesis of these cancers. Their differential expression in HPV-positive HNSCC may mechanistically contribute to the genesis and clinical characteristics of these cancers, making them attractive targets for immunotherapies. These antigens, historically linked to diverse cancers, are increasingly implicated in various hallmarks of cancer, suggesting potential as cancer drivers.
Article
Genetics & Heredity
Yaodong He, Yunshan Li, Junwei Xiang, Xu Huang, Mingyu Zhao, Yuanyin Wang, Ran Chen
Summary: Tyrosine kinase 2 (TYK2) is overexpressed in head and neck squamous cell carcinoma (HNSCC) and is associated with tumor growth, prognosis, and immune infiltration. TYK2 can serve as a novel biomarker for assessing the prognosis of HNSCC patients and aiding in immunotherapy against HNSCC.
FRONTIERS IN GENETICS
(2022)
Article
Dentistry, Oral Surgery & Medicine
Jingyi Luo, Yuejiao Huang, Jiahe Wu, Lin Dai, Mingyou Dong, Bo Cheng
Summary: An 8 hypoxia-associated gene signature was established as a novel independent prognostic indicator for HNSCC patients. The nomogram combining the risk score and clinical stage showed enhanced predictive performance compared to the risk model alone. Significant differences in immune cell infiltration levels and metabolic pathways were found between high and low risk subgroups.
Review
Oncology
Tycho de Bakker, Fabrice Journe, Geraldine Descamps, Sven Saussez, Tatiana Dragan, Ghanem Ghanem, Mohammad Krayem, Dirk Van Gestel
Summary: TP53 mutation is a common genetic alteration in head and neck squamous cell carcinoma (HNSCC), and targeting p53 for therapy shows potential. Therapeutic strategies can be categorized into targeting wild-type p53 degradation or inhibition, directly affecting mutated p53, and specifically targeting HPV-positive HNSCC. This review discusses p53 regulation and its targeting in combination with existing therapies, based on the classification of HNSCC according to p53 mutation status and HPV infection.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Xiuping Yang, Baoai Han, Runshi Zhang, Yuan Su, Davood K. Hosseini, Han Wu, Minlan Yang, Haiying Sun
Summary: Defects in RNA-binding proteins (RBPs) are closely associated with the occurrence and development of HNSCC. A prognostic model containing nine RBPs was constructed, and these RBPs were found to play important roles in the overall survival of HNSCC patients.
Article
Genetics & Heredity
Yaoxu Li, Yinpei Huang, Bing Li, Kai Yang
Summary: This study found that the expression levels of E2Fs genes were significantly elevated in head and neck squamous cell carcinoma (HNSCC). E2F1, E2F3, E2F4, E2F6, and E2F7 were identified as reliable diagnostic markers. High expression of E2F6 was associated with poor prognosis in female HNSCC patients.
BMC MEDICAL GENOMICS
(2023)
Article
Immunology
Ying Xiong, Yu Si, Yisi Feng, Shipei Zhuo, Bozhen Cui, Zhigang Zhang
Summary: In this study, a total of 136 differentially expressed lipid metabolism genes were identified in head and neck squamous cell carcinoma (HNSCC), with 23 of them related to prognosis. Additionally, 11 lipid metabolism-related genes were found to affect clinical features of HNSCC, such as stage, gender, and pathological stage. The prognostic index of lipid metabolism-related genes reflected the state of the HNSCC tumor immune microenvironment.
IMMUNITY INFLAMMATION AND DISEASE
(2021)
Article
Oncology
Marc-Andre Gauthier, Adway Kadam, Gary Leveque, Nahid Golabi, Anthony Zeitouni, Keith Richardson, Marco Mascarella, Nader Sadeghi, Sampath Kumar Loganathan
Summary: HPV plays a significant role in oropharyngeal squamous cell carcinoma, and long-read sequencing technology can effectively assess HPV integration patterns. Further research is needed on the prognostic value of high-risk HPV integration in OPSCC using long-read sequencing technology.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Dina Hingorani, Michael M. Allevato, Maria F. Camargo, Jacqueline Lesperance, Maryam A. Quraishi, Joseph Aguilera, Ida Franiak-Pietryga, Daniel J. Scanderbeg, Zhiyong Wang, Alfredo A. Molinolo, Diego Alvarado, Andrew B. Sharabi, Jack D. Bui, Ezra E. W. Cohen, Stephen R. Adams, J. Silvio Gutkind, Sunil J. Advani
Summary: The authors show that the combination of monomethyl auristatin and radiotherapy can promote anti-tumor immune responses and improve the response to checkpoint inhibitors in cancer therapy. This trimodal precision cytotoxic chemo-radio-immunotherapy paradigm has the potential to improve tumor control and patient outcomes.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Robert Saddawi-Konefka, Shiruyeh Schokrpur, Asona J. Lui, J. Silvio Gutkind
Summary: Research has shown that abnormalities in the ErbB signaling pathways play a crucial role in oncogenesis, and efforts to target these aberrations offer great potential in treating various types of cancer. While the focus has primarily been on the EGFR pathway, recent studies have identified significant dysregulation in the HER2 and HER3 signaling pathways in head and neck cancer. This review highlights clinical efforts to target these receptors and their aberrant signaling, including the use of small molecule inhibitors and blocking antibodies, in the treatment of head and neck squamous cell carcinomas and other malignancies.
Article
Oncology
Kris C. Wood, J. Silvio Gutkind
Article
Biochemistry & Molecular Biology
Nicolas A. Pinto, Martin C. Abba, Lorena Laporte, Juan M. Perez M. Saez, Ada G. G. Blidner, Nicolas I. Torres, Rosa M. M. Morales, Sabrina G. G. Gatto, Camila A. A. Bach, Florencia Veigas, Hernan J. Garcia Rivello, Peng Song, Jane H. H. Frederiksen, Lene Juel Rasmussen, Francoise Poirier, Diego O. O. Croci, Victoria Sundblad, Gabriel A. A. Rabinovich, Juan P. P. Cerliani
Summary: Non-melanoma skin cancer (NMSC) has increased due to chronic exposure to sunlight, climatic changes, and immunosuppression. Gal-7, a protein expressed in skin tissue, plays a critical role in NMSC development. Overexpression of Gal-7 leads to an increase in the number of papillomas in transgenic mice.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Nadia Arang, Simone Lubrano, Damiano Cosimo Rigiracciolo, Daniela Nachmanson, Scott M. Lippman, Prashant Mali, Olivier Harismendy, J. Silvio Gutkind
Summary: G proteins and G protein-coupled receptors activate signal transduction pathways that promote cell growth and survival. This study found that G alpha q promotes PI3K/AKT signaling pathway activation, leading to resistance to FAK inhibition. These findings establish a novel link between G alpha q-driven signaling and the stimulation of PI3K, demonstrating the aberrant activation of signaling networks underlying the growth and survival of UM and other G alpha q-driven malignancies.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Oncology
Alison E. Smith, Stacia Chan, Zhiyong Wang, Asako Mccloskey, Quinn Reilly, Jayden Z. Wang, Hetika Vora Patel, Keiichi Koshizuka, Harris S. Soifer, Linda Kessler, Ashley Dayoub, Victoria Villaflor, Douglas R. Adkins, Justine Y. Bruce, Alan L. Ho, Cesar A. Perez, Glenn J. Hanna, Amaya Gasco Hernandez, Andrew Saunders, Stephen Dale, J. Silvio Gutkind, Francis Burrows, Shivani Malik
Summary: The outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) are poor, and there are limited treatment options for those who progress on standard-of-care immunotherapy. Researchers have developed a combination therapy targeting the key drivers of HNSCC, PI3K-mTOR and HRAS, using the inhibitors tipifarnib and alpelisib. This combination therapy has shown promise in preclinical studies and early clinical trials, with potential to benefit over 45% of patients with recurrent/metastatic HNSCC. Additionally, tipifarnib may enhance the effectiveness of other targeted therapies by preventing adaptive resistance.
Article
Oncology
Sankar Jagadeeshan, Manu Prasad, Mai Badarni, Talal Ben-Lulu, Vijayasteltar Belsamma Liju, Sooraj Mathukkada, Claire Saunders, Avital Beeri Shnerb, Jonathan Zorea, Ksenia M. Yegodayev, Monica Wainer, Liza Vtorov, Irit Allon, Ofir Cohen, Gro Gausdal, Dinorah Friedmann-Morvinski, Sok Ching Cheong, Alan L. Ho, Ari J. Rosenberg, Linda Kessler, Francis Burrows, Dexin Kong, Jennifer R. Grandis, J. Silvio Gutkind, Moshe Elkabets
Summary: The presence of mutated HRAS in head and neck cancer patients is associated with poor prognosis and high metastasis rate. Mutated HRAS promotes cancer cell invasion and metastasis by suppressing the Hippo pathway and promoting AXL expression. The use of tipifarnib, a farnesyltransferase inhibitor, can activate the Hippo pathway, suppress metastasis, and regulate angiogenesis in HNC.
Review
Oncology
Raphaelly Venzel, Maria Clara Paulino Campos, Larissa Pessoa de Oliveira, Rodrigo Vasquez Dan Lins, Adamo Davi Diogenes Siena, Kim Tavares Mesquita, Talita Pollyana Moreira dos Santos, Nijiro Nohata, Lucas Coelho Marliere Arruda, Helioswilton Sales-Campos, Marinaldo Pacifico Cavalcanti Neto
Summary: Traditional therapeutic approaches for malignant melanoma have limitations and ineffectiveness in improving patient survival and tumor recurrence. Immunotherapy, as a promising alternative, modulates cell signaling pathways involved in the immune system's effector mechanisms, known as immunological checkpoints, to boost antitumor responses. Clinical studies on immunotherapeutic regimens have shown encouraging results in recent decades. This review discusses current immunotherapeutic regimens, molecular and cellular mechanisms, and clinical studies of immunotherapy in melanoma.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Shuo Wang, Zhi-Zhong Wu, Su-Wen Zhu, Shu-Cheng Wan, Meng-Jie Zhang, Bo-Xin Zhang, Qi-Chao Yang, Yao Xiao, Hao Li, Liang Mao, Zhi-Yong Wang, J. Silvio Gutkind, Zhi-Jun Sun
Summary: Immune checkpoint blockade (ICB) treatment is effective in oncology, but has limitations including low response rates and a lack of efficacy predictors. Gasdermin protein expression is associated with a favorable tumor immune microenvironment and prognosis in head and neck squamous cell carcinoma. CTLA-4 blockade treatment induces gasdermin-mediated pyroptosis of tumor cells, with gasdermin expression correlating with treatment effectiveness. CTLA-4 blockade activates CD8+ T cells and increases levels of IFN-g and TNF-a cytokines, triggering tumor cell pyroptosis and release of inflammatory substances and chemokines.
Article
Immunology
Victoria H. Wu, Bryan S. Yung, Farhoud Faraji, Robert Saddawi-Konefka, Zhiyong Wang, Alexander T. Wenzel, Miranda J. Song, Meghana S. Pagadala, Lauren M. Clubb, Joshua Chiou, Sanju Sinha, Marin Matic, Francesco Raimondi, Thomas S. Hoang, Rebecca Berdeaux, Dario A. A. Vignali, Ramiro Iglesias-Bartolome, Hannah Carter, Eytan Ruppin, Jill P. Mesirov, J. Silvio Gutkind
Summary: The authors used computational screening and chemogenetic analysis of transgenic mice to show that G alpha(s)-coupled G-protein-coupled receptors (GPCRs) on exhausted CD8(+) T cells play a role in suppressing effector functions and inhibiting the protective effects of immune checkpoint immunotherapy. They found an enrichment of G alpha(s)-coupled GPCRs on exhausted CD8(+) T cells and identified several specific receptors that promote T cell dysfunction. By activating the G alpha(s) signaling axis, they demonstrated that CD8(+) T cell dysfunction and immunotherapy failure can be promoted. These findings suggest that G alpha(s)-GPCRs could be targeted to enhance the response to immune checkpoint blockade immunotherapies.
Article
Biochemistry & Molecular Biology
Natalie Hewitt, Ning Ma, Nadia Arang, Sarah A. Martin, Ajit Prakash, Jeffrey F. DiBerto, Kevin M. Knight, Soumadwip Ghosh, Reid H. J. Olsen, Bryan L. Roth, J. Silvio Gutkind, Nagarajan Vaidehi, Sharon L. Campbell, Henrik G. Dohlman
Summary: Heterotrimeric guanine nucleotide-binding proteins (G proteins) act as molecular switches for cellular growth and metabolism. Mutations in the glutamine residue critical for GTP hydrolysis in the G protein alpha subunit are common in uveal melanoma. Our study reveals that these mutations have functional diversity and contribute to G protein functions beyond GTP hydrolysis.
Article
Multidisciplinary Sciences
Meghana Pagadala, Timothy J. Sears, Victoria H. Wu, Eva Perez-Guijarro, Hyo Kim, Andrea Castro, James V. Talwar, Cristian Gonzalez-Colin, Steven Cao, Benjamin J. Schmiedel, Shervin Goudarzi, Divya Kirani, Jessica Au, Tongwu Zhang, Teresa Landi, Rany M. Salem, Gerald P. Morris, Olivier Harismendy, Sandip Pravin Patel, Ludmil B. Alexandrov, Jill P. Mesirov, Maurizio Zanetti, Chi-Ping Day, Chun Chieh Fan, Wesley K. Thompson, Glenn Merlino, J. Silvio Gutkind, Pandurangan Vijayanand, Hannah Carter
Summary: Understanding how host genetics affects the tumor immune microenvironment (TIME) is essential for personalized cancer screening and treatment strategies. A study analyzed the eQTLs affecting TIME and found that they are enriched in areas of active transcription and associated with gene expression in specific immune cell subsets. Polygenic score models built with TIME eQTLs can stratify cancer risk, survival, and immune checkpoint blockade (ICB) response. Inhibiting the CTSS gene, which is implicated by the polygenic models, slows tumor growth and extends survival, suggesting the potential of integrating genetic factors and TIME characteristics for immunotherapy targets.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Soledad Iseas, Diego Prost, Sarah Bouchereau, Mariano Golubicki, Juan Robbio, Ana Oviedo, Mariana Coraglio, Mirta Kujaruk, Guillermo Mendez, Marcela Carballido, Enrique Roca, Louis Gros, Vincent De Parades, Nabil Baba-Hamed, Julien Adam, Martin Carlos Abba, Eric Raymond
Summary: This retrospective study analyzed the clinical data of 176 patients with anal squamous cell carcinoma who completed chemoradiotherapy. Complete response was found to be predictive of disease-free survival and overall survival. Other prognostic factors included tumor stage, lymph node metastasis, sex, differentiation status, tumor location, and HIV-HPV coinfection. These results provide important insights for the treatment and prognosis evaluation of anal squamous cell carcinoma.
Article
Oncology
Ana Ruiz-Saenz, Chloe E. Atreya, Changjun Wang, Bo Pan, Courtney A. Dreyer, Diede Brunen, Anirudh Prahallad, Denise P. Munoz, Dana J. Ramms, Valeria Burghi, Danislav S. Spassov, Eleanor Fewings, Yeonjoo C. Hwang, Cynthia Cowdrey, Christina Moelders, Cecilia Schwarzer, Denise M. Wolf, Byron Hann, Scott R. VandenBerg, Kevan Shokat, Mark M. Moasser, Rene Bernards, J. Silvio Gutkind, Laura J. van 't Veer, Jean-Philippe Coppe
Summary: Coppe and colleagues discover a resistance mechanism in BRAF(V600E) colorectal cancers that can be overcome with COX2 inhibitors. SRC kinases play a role in resistance to BRAF/EGFR-targeted therapy and can be effectively targeted in combination with BRAF and EGFR. Compensatory activation of SRC kinases is mediated by an autocrine prostaglandin E-2 loop, which can be blocked with COX2 inhibitors. Co-targeting COX2, BRAF, and EGFR promotes long-lasting suppression of tumor growth in patient-derived tumor xenograft models.
Article
Biochemistry & Molecular Biology
Valeria Burghi, Justine S. Paradis, Adam Officer, Sendi Rafael Adame-Garcia, Xingyu Wu, Edda S. F. Matthees, Benjamin Barsi-Rhyne, Dana J. Ramms, Lauren Clubb, Monica Acosta, Pablo Tamayo, Michel Bouvier, Asuka Inoue, Mark von Zastrow, Carsten Hoffmann, J. Silvio Gutkind
Summary: This study focuses on the role of beta-arrestins in G protein-coupled receptor (GPCR) signaling. It is found that while G proteins are essential for GPCR signaling, beta-arrestins play a more prominent role in signal compartmentalization and modulation of gene expression.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Oncology
Vanita Noronha, Aditya Dhanawat, Vijay Maruti Patil, Nandini Menon, Ajay Kumar Singh, Pankaj Chaturvedi, Prathamesh Pai, Devendra Chaukar, Sarbani Ghosh Laskar, Kumar Prabhash
Summary: Neo-adjuvant chemotherapy has shown long term survival benefits in patients with locally advanced oral cavity squamous cell carcinomas.
Article
Oncology
Andrea Costantino, Claudio Sampieri, Gian Marco Pace, Bianca Maria Festa, Luca Cerri, Giorgio Gregory Giordano, Michael Dale, Giuseppe Spriano, Giorgio Peretti, Armando De Virgilio
Summary: This study aimed to predict the necessity of enteral nutrition at 28 days after surgery in patients with head and neck cancers. The results showed that the machine learning models had optimistic accuracy in predicting the need for enteral nutrition, but had moderate sensitivity.
Article
Oncology
Lirui Zhang, Qiaoshi Xu, Zhien Feng
Summary: This study presents a comprehensive clinical, genomic, and transcriptomic analysis of primary ghost cell odontogenic carcinoma (GCOC). The results provide the first comprehensive molecular atlas for primary GCOC, including previously identified CTNNB1 mutation and novel alterations in MAP3K, EP300, and the 22q11.21 region. The transcriptome analysis reveals significant involvement of cytokine-cytokine receptor interaction and the PI3K-Akt signaling pathway. More GCOC cases should be compared to validate these findings for accurate clinical guidance.
Article
Oncology
Emily Capone, Vittoria Perrotti, Ilaria Cela, Rossano Lattanzio, Lucrezia Togni, Corrado Rubini, Vito Carlo Alberto Caponio, Lorenzo Lo Muzio, Martina Colasante, Francesco Giansanti, Rodolfo Ippoliti, Stefano Iacobelli, Michael J. Wick, Nicole Spardy Burr, Gianluca Sala
Summary: This study explores the potential of galectin-3 binding protein (LGALS3BP) as a novel target for antibody-drug conjugate (ADC) therapy in adenoid cystic carcinoma (ACC). The results show that LGALS3BP is highly expressed in ACC tissues and treatment with anti-LGALS3BP ADC leads to durable tumor growth inhibition in animal models.
Article
Oncology
Andrea Costantino, Claudio Sampieri, Piero Giuseppe Meliante, Armando De Virgilio, Se-Heon Kim
Summary: This study compares the outcomes of transoral resections using the da Vinci SP and da Vinci Xi systems for oropharyngeal squamous cell carcinoma (OPSCC). The results indicate that the da Vinci SP system has advantages in terms of reduced docking and console times, as well as improved rates of wide negative resection margins. However, there were no significant differences in complication rates or postoperative functional outcomes between the two systems.
