Opportunities and challenges facing biomarker development for personalized head and neck cancer treatment

Lucs, Alexandra V.; Saltman, Benjamin; Chung, Christine H.; Steinberg, Bettie M.; Schwartz, David L.

doi:10.1002/hed.21975

Cited by 19 publications

(23 citation statements)

References 198 publications

(203 reference statements)

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“…Importantly, although the ML phenotype has been consistently associated with poor outcome, tumors displaying an epithelial‐like (EL) phenotype show widely diverse clinical behavior. Supporting this argument, genome‐wide association studies and gene expression analyses have identified distinct tumor subtypes, apart from ML tumors, which maintain EL features . The identification of specific markers able to stratify tumors sharing an EL phenotype would be helpful in identifying patients with a high risk of recurrence …”

Section: Introductionmentioning

confidence: 99%

The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes

et al. 2019

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Background We aimed at identifying molecular markers predictive of clinical outcome in patients with head and neck cancer based on the expression profile of cells showing epithelial‐like (EL) or mesenchymal‐like (ML) phenotypes. Materials and methods We analyzed the association between EL and ML cells and migration, drug resistance, or tumor growth. The differential gene expression profile between cell types was used to build a model to stratify patients according to survival. Results EL cells were sensitive to cisplatin and cetuximab, showed low migration, and generated squamous differentiated tumors in mouse. A differential 93‐gene expression signature between ML and EL cells was used to build a three‐gene (EFS, GPX2, and SPRR1A) survival model by analyzing the RNA‐seq data of the TCGA‐HNSC project. Its prognostic value was confirmed in two independent cohorts. Conclusion EFS, GPX2, and SPRR1A are prognostic markers able to distinguish clinical outcome among subtypes sharing an EL phenotype.

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Section: Introductionmentioning

confidence: 99%

The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes

et al. 2019

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“…This represents an important facet and usage for PDXs, especially for cancers such as head and neck squamous cell carcinoma (HNSCC) where no currently validated predictive biomarkers exist. [8]…”

Section: Introductionmentioning

confidence: 99%

Defining the boundaries and expanding the utility of head and neck cancer patient derived xenografts

et al. 2017

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Background Patient derived xenografts (PDXs) represent an essential tool in oncologic research, and we sought to further expand our repertoire of head and neck squamous cell carcinoma (HNSCC) while determining potential boundaries for this system. Methods We consented new patients for PDX development and determined if a 24-hour time delay from tumor excision to xenograft implantation affected PDX establishment. We developed a tissue microarray (TMA) from formalin fixed, paraffin embedded PDXs and their subsequent passages and carried out quantitative immunohistochemistry for EGFR, pEGFR, pAkt, pERK and ERCC1. First and last passaged PDXs were compared via a paired t-test to examine for the stability of protein expression across passages. We performed a similar comparison of the mutational profile of the patient tumor and resulting xenografts using a targeted sequencing approach. Results No patient/tumor characteristics influenced PDX take rate and the 24-hour time delay from tumor excision to xenograft implantation did not affect PDX establishment, growth or histology. There was no significant difference in biomarker expression between the first and last passaged PDXs for EGFR, pEGFR, pAkt, and ERCC1. For pERK there was a significant difference (p=0.002), but further analysis demonstrated this only arose in three of 15 PDXs. Targeted sequencing revealed striking stability of passenger and likely driver mutations from patient to xenograft. Conclusions The stability of protein expression across PDX passages will hopefully allow greater investigation of predictive biomarkers in order to identify ones for further pre-clinical and clinical investigation.

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“…Every year Ͼ42,000 cases of oral, laryngeal, and pharyngeal cancer are diagnosed and Ͼ12,000 individuals die of the disease (3). The diagnosis and treatment of head and neck cancer presents several unique challenges.…”

mentioning

confidence: 99%

p16 Protein and Gigaxonin Are Associated with the Ubiquitination of NFκB in Cisplatin-induced Senescence of Cancer Cells

Veena

Wilken

Zheng

et al. 2014

Journal of Biological Chemistry

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Background: Molecular mechanism of p16-mediated cellular senescence in cisplatin-treated cells is not known. Results: Cisplatin treatment leads to p16 nuclear transport and association with gigaxonin for the ubiquitination of NFB. Conclusion: A protein associated with neural diseases is involved in cisplatin-mediated cellular senescence. Significance: Nuclear expression of p16 and gigaxonin is a useful marker of cancer cell chemosensitivity.

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Opportunities and challenges facing biomarker development for personalized head and neck cancer treatment

Cited by 19 publications

References 198 publications

The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes

The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes

Defining the boundaries and expanding the utility of head and neck cancer patient derived xenografts

p16 Protein and Gigaxonin Are Associated with the Ubiquitination of NFκB in Cisplatin-induced Senescence of Cancer Cells

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