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Acquired resistance to immunotherapy and chemoradiation in MYC amplified head and neck cancer.
Cyberski, Thomas F; Singh, Alka; Korzinkin, Michael; Mishra, Vasudha; Pun, Frank; Shen, Le; Wing, Claudia; Cheng, Xiangying; Baird, Brandon; Miao, Yuxuan; Elkabets, Moshe; Kochanny, Sara; Guo, Wenji; Dyer, Emma; Pearson, Alexander T; Juloori, Aditya; Lingen, Mark; Cole, Grayson; Zhavoronkov, Alex; Agrawal, Nishant; Izumchenko, Evgeny; Rosenberg, Ari J.
Afiliación
  • Cyberski TF; Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.
  • Singh A; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
  • Korzinkin M; Insilico Medicine, Pak Shek Kok, Hong Kong.
  • Mishra V; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
  • Pun F; Insilico Medicine, Pak Shek Kok, Hong Kong.
  • Shen L; Department of Surgery, University of Chicago, Chicago, IL, USA.
  • Wing C; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
  • Cheng X; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
  • Baird B; Department of Surgery, University of Chicago, Chicago, IL, USA.
  • Miao Y; Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
  • Elkabets M; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University, Beer Sheva, Israel.
  • Kochanny S; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
  • Guo W; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
  • Dyer E; Harvard T.H. Chan School of Public Health, Cambridge, MA, USA.
  • Pearson AT; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
  • Juloori A; Department of Radiation Oncology, University of Chicago, Chicago, IL, USA.
  • Lingen M; Department of Pathology, University of Chicago, Chicago, IL, USA.
  • Cole G; Department of Pathology, University of Chicago, Chicago, IL, USA.
  • Zhavoronkov A; Insilico Medicine, Pak Shek Kok, Hong Kong.
  • Agrawal N; Department of Surgery, University of Chicago, Chicago, IL, USA.
  • Izumchenko E; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA. izumchen@uchicago.edu.
  • Rosenberg AJ; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA. arirosenberg@uchicago.edu.
NPJ Precis Oncol ; 8(1): 114, 2024 May 23.
Article en En | MEDLINE | ID: mdl-38783041
ABSTRACT
The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated. Here we present a unique case of a patient with recurrent/metastatic (R/M) HNSCC who, despite initial response to nivolumab-based treatment, developed rapidly progressive metastatic disease after the acquisition of MYC amplification. We conducted comparative transcriptomic analysis of this patient's tumor at baseline and upon progression to interrogate potential molecular processes through which MYC may confer resistance to immunotherapy and/or chemoradiation and used TCGA-HNSC dataset and an institutional cohort to further explore clinicopathologic features and key molecular networks associated with MYC amplification in HNSCC. This study highlights MYC amplification as a potential mechanism of immune checkpoint inhibitor resistance and suggest its use as a predictive biomarker and potential therapeutic target in R/M HNSCC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Precis Oncol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Precis Oncol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido