Publications by authors named "Chad Brenner"

Article Synopsis
  • * Recent research used advanced genetic sequencing techniques to uncover a new fusion gene (CRTC1::MAML2) and a surprising rearrangement of the MAML2 gene to MYBL1, hinting at MYBL1's potential role in salivary gland cancers.
  • * The study also found that TERT gene rearrangements and amplifications are common in MEC tumors, with TERT playing a crucial role in tumor growth, as demonstrated
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Background: Post-treatment surveillance recommendations for oropharyngeal cancer do not vary with p16 status despite the differences in outcomes. The optimal algorithm personalizing follow-up for these patients remains undefined. Here, we evaluate the feasibility and utility of incorporating electronic patient-reported outcomes (ePROs) and circulating tumor DNA (ctDNA) into routine surveillance for patients treated for p16+ oropharynx cancer.

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BACKGROUNDTransrenal cell-free tumor DNA (TR-ctDNA), which transits from the bloodstream into urine, has the potential to enable noninvasive cancer detection for a wide variety of nonurologic cancer types.MethodsUsing whole-genome sequencing, we discovered that urine TR-ctDNA fragments across multiple cancer types are predominantly ultrashort (<50 bp) and, therefore, likely to be missed by conventional ctDNA assays. We developed an ultrashort droplet digital PCR assay to detect TR-ctDNA originating from HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) and confirmed that assaying ultrashort DNA is critical for sensitive cancer detection from urine samples.

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Background: Head and neck squamous cell carcinoma (HNSCC) is a lethal disease with poor survival rates, especially for cancers arising in the oral cavity or larynx. Cisplatin is a key chemotherapeutic for HNSCC; however poor survival rates may be partially due to cisplatin resistance observed in some HNSCCs. Here, we examined the utility of genome-wide CRISPR knockout profiling for nominating pivotal mechanisms of cisplatin resistance in HNSCC models.

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Background: Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease with poor survival rates. While the epidermal growth factor receptor (EGFR)-targeting antibody Cetuximab is approved for treatment, responses are limited and the molecular mechanisms driving resistance remain incompletely understood.

Methods: To better understand how cells survive without EGFR activity, we developed an EGFR knockout derivative of the UM-SCC-92 cell line using CRISPR/Cas9 technology.

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Importance: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma has an overall favorable prognosis, yet a subset of patients will experience devastating disease recurrence. Current surveillance standards for detection of recurrent disease are imperfect. There is growing interest in improving detection of recurrent disease through the use of plasma-based assays able to detect circulating tumor HPV DNA.

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Article Synopsis
  • Head and neck squamous cell carcinomas (HNSCC) have high treatment-related complications and poor survival rates, particularly in recurrent or metastatic cases, with PD-1/PD-L1 inhibitors now being a primary treatment option.
  • A study identified 335 genes that enhance PD-L1 expression in HNSCC cells, validating five specific genes (FGF6, IL17A, CD300C, KLR1C, NFKBIA) as key drivers, with FGF ligand being a significant factor in this regulation.
  • The research suggests that FGF signaling promotes immune evasion through PD-L1 upregulation, indicating potential for new combination therapies to improve treatment effectiveness against
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Head and neck squamous cell carcinomas (HNSCCs) are often associated with poor outcomes, due at least in part to the limited number of treatment options available for those patients who develop recurrent and/or metastatic disease (R/M HNSCC). Even with the recent validation and approval of immunotherapies in the first-line setting for these patients, the need for the development of new and alternative precision medicine strategies with survival benefit is clear. Oncogenic alterations in the HRAS (Harvey rat sarcoma virus) proto-oncogene are seen in approximately 4-8% of R/M HNSCC tumors.

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Hypoxia in head and neck tumors has proven to be predictive of outcomes. Current hypoxia signatures have failed for patient treatment selection. In a recent study, the authors identified a hypoxia methylation signature as a more robust biomarker in head and neck squamous cell carcinoma and shed light into the mechanism of hypoxia-mediated treatment resistance.

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Objectives: To develop a high-performance droplet digital PCR (ddPCR) assay capable of enhancing the detection of human papillomavirus (HPV) circulating tumor DNA (ctDNA) in plasma from patients with HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC).

Materials And Methods: Plasma samples from subjects with HPV+ OPSCC were collected. We developed a high-performance ddPCR assay designed to simultaneously target nine regions of the HPV16 genome.

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Article Synopsis
  • A study analyzed patterns of recurrence and survival in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) from 1998 to 2019, involving 447 patients.!
  • Median overall survival improved from 6.7 months (1998-2007) to 11.8 months (2008-2019), with factors like HPV negativity and poor performance status linked to worse outcomes.!
  • The findings support the importance of early detection for recurrence and suggest that understanding these patterns can help develop personalized follow-up care and guide clinical trial eligibility.
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Background: We sought to characterize early changes in CD8 tumor-infiltrating lymphocytes and tumor transcriptomes after induction cetuximab in a cohort with p16-positive oropharyngeal cancer on a phase II clinical de-escalation trial.

Methods: Tumor biopsies were obtained before and 1 week after a single cetuximab loading dose in eight patients enrolled in a phase II trial of cetuximab and radiotherapy. Changes in CD8 tumor-infiltrating lymphocytes and transcriptomes were assessed.

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Purpose: F-Fluorodeoxyglucose positron emission tomography (FDG-PET) parameters are prognostic of oncologic outcomes in human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). We used FDG-PET imaging biomarkers to select patients for de-escalated chemoradiotherapy (CRT), hypothesizing that acute toxicity will be improved with de-escalation.

Methods And Materials: This is a planned interim initial feasibility and acute toxicity report from a phase 2, prospective, nonrandomized study, which enrolled patients with stage I-II p16+ OPSCC.

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Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillomavirus (HPV) as a potential driver of mucoepidermoid carcinoma.

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Objectives: In an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery.

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Purpose: We conducted a randomized phase II multicenter clinical trial to test the hypothesis that physiologic MRI-based radiotherapy (RT) dose escalation would improve the outcome of patients with poor prognosis head and neck cancer.

Patients And Methods: MRI was acquired at baseline and at RT fraction 10 to create low blood volume/apparent diffusion coefficient maps for RT boost subvolume definition in gross tumor volume. Patients were randomized to receive 70 Gy (standard RT) or 80 Gy to the boost subvolume (RT boost) with concurrent weekly platinum.

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Translational research describes the process of applying observations and scientific discoveries made in the laboratory to clinical applications that can improve the health of individual patients, most often through clinical trials. To apply the findings of translational research studies to the broader population, the study population must accurately reflect the group of patients afflicted by a particular disease. Yet, it is well known that significant disparities exist for underrepresented groups and lower socioeconomic populations in clinical trials.

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Cancer biomarkers are a promising tool for cancer detection, personalization of therapy, and monitoring of treatment response or recurrence. "Liquid biopsy" commonly refers to minimally invasive or non-invasive sampling of a bodily fluid (i.e.

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Background: The genomic frontier continues to revolutionize the practice of oncology. Advances in cancer biology from tumorigenesis to treatment resistance are driven by the molecular underpinnings of malignancy. The framing of precision oncology as both a clinical and research tool is constantly evolving and directly influences conversations between oncologists and their patients.

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Article Synopsis
  • - HNSCC is a challenging disease with limited treatment success; cetuximab can help some patients but isn’t effective for everyone, indicating the need for new treatment strategies.
  • - Researchers conducted a drug screen to find effective combinations of EGFR inhibitors with other drugs, particularly focusing on cases resistant to single EGFR inhibitors.
  • - The study revealed both known effective combinations and new ones, which highlights the necessity for future testing and the potential development of diagnostic tools to improve patient outcomes.
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Human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) is associated with improved outcomes compared to non-virally mediated disease. Clinical trials are actively investigating de-escalation strategies to maintain excellent survival outcomes while minimizing toxicity. Delivery of effective precision medicine-based therapeutic approaches are strengthened by the identification of biomarkers to predict treatment response.

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Head and Neck cancer survival has continued to remain around 50% despite treatment advances. It is thought that cancer stem cells play a key role in promoting tumor heterogeneity, treatment resistance, metastasis, and recurrence in solid malignancies including head and neck cancer. Initial studies identified cancer stem cell markers including CD44 and ALDH in head and neck malignancies and found that these cells show aggressive features in both and studies.

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