Pritzker School of Medicine
Published May 23, 2024 | Version v1
Journal article Open

Acquired resistance to immunotherapy and chemoradiation in MYC amplified head and neck cancer

Creators

  • 1. University of Chicago
  • 2. Insilico Medicine
  • 3. Ben-Gurion University
  • 4. Harvard University

Description

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.

Data availability

The authors declare that the data supporting the findings of this study are available within the article and its supplementary information files. Source data are provided with this paper. Patients' de-identified data (such as diagnosis, gender, averaged age, and treatment type) is provided in the manuscript.

No code was developed in this study. GSEA software is freely available for download at https://www.gsea-msigdb.org/gsea/index.jsp. PandaOmics is industry-grade commercial software platform used since 2020. The platform is available at https://pandaomics.com. A trial access to the platform is available from InSilico Medicine upon request. A workflow for running the platforms is described in the "Methods" section.

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Acquired-resistance-to-immunotherapy-and-chemoradiation-in-MYC-amplified-head-and-neck-cancer.pdf

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Additional details

Identifiers

DOI
10.1038/s41698-024-00606-w
Other
oai:uchicago.tind.io:12059

Funding

National Institutes of Health
R01DE027809
National Institutes of Health
R01DE028674
Burroughs Wellcome Fellowship

UChicago Information

Division(s)
Biological Sciences Division, Pritzker School of Medicine
Department(s)
Ben May Department for Cancer Research, Medicine, Pathology, Radiation and Cellular Oncology, Surgery