Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma

Huang, Chen; Chen, Lijun; Savage, Sara R.; Eguez, Rodrigo Vargas; Dou, Yongchao; Li, Yize; Leprevost, Felipe da Veiga; Jaehnig, Eric J.; Lei, Jonathan T.; Wen, Bo; Schnaubelt, Michael; Krug, Karsten; Song, Xiaoyu; Cieślik, Marcin; Chang, Hui-Yin; Wyczalkowski, Matthew A.; Li, Kai; Colaprico, Antonio; Li, Qing Kay; Clark, David; Hu, Yingwei; Cao, Liwei; Pan, Jianbo; Wang, Yuefan; Cho, Kyung-Cho; Shi, Zhiao; Liao, Yuxing; Jiang, Wen; Anurag, Meenakshi; Ji, Jiayi; Yoo, Seungyeul; Zhou, Daniel Cui; Liang, Wen-Wei; Wendl, Michael C.; Vats, Pankaj; Carr, Steven A.; Mani, D. R.; Zhang, Zhen; Qian, Jiang; Chen, Xi S.; Pico, Alexander; Wang, Pei; Chinnaiyan, Arul M.; Ketchum, Karen A.; Kinsinger, Christopher R.; Robles, Ana I.; An, Eunkyung; Hiltke, Tara; Mesri, Mehdi; Thiagarajan, Mathangi; Weaver, Alissa M.; Sikora, Andrew G.; Lubiński, Jan; Wierzbicka, Małgorzata; Wiznerowicz, Maciej; Satpathy, Shankha; Gillette, Michael A.; Miles, George; Ellis, Matthew J.; Omenn, Gilbert S.; Rodriguez, Henry; Boja, Emily S.; Dhanasekaran, Saravana M.; Li, Ding; Nesvizhskii, Alexey I.; El‐Naggar, Adel K.; Chan, Daniel W.; Zhang, Hui; Zhang, Bing; Agarwal, Anupriya; Anderson, Matthew L.; Avanessian, Shayan C.; Avtonomov, Dmitry M.; Bathe, Oliver F.; Birger, Chet; Birrer, Michael J.; Blumenberg, Lili M.; Bocik, William; Borate, Uma; Borucki, Melissa; Burke, Meghan C.; Cai, Shuang; Calinawan, Anna; Cerda, Sandra; Charamut, Alyssa; Chen, Lin S.; Chowdhury, Shrabanti; Clauser, Karl R.; Culpepper, Houston; Czernicki, Tomasz; D’Angelo, Fulvio; Day, Jacob; Young, Stephanie; Demir, Emek; Ding, Fei; Domagalski, Marcin J.; Dort, Joseph C.; Druker, Brian J.; Duffy, Elizabeth; Dyer, Maureen A.; Edwards, Nathan; Elburn, Kimberly; Ermakova, Tatiana S.; Fenyö, David; Ferrarotto, Renata; Francis, Alicia; Gabriel, Stacey; Garofano, Luciano; Geffen, Yifat; Getz, Gad; Goldthwaite, Charles A.; Hannick, Linda; Hariharan, Pushpa; Hayes, D. Neil; Heiman, David I.; Hindenach, Barbara; Hoadley, Katherine A.; Hostetter, Galen; Hyrcza, Martin; Jewell, Scott D.; Jones, Corbin D.; Kane, M. Harry; Karz, Alicia; Kothadia, Ramani B.; Krek, Azra; Kumar-Sinha, Chandan; Liu, Tao; Liu, Hongwei; Ma, Wanli; Malc, Ewa; Malovannaya, Anna; Mareedu, Sailaja; Markey, Sanford P.; Marrero-Oliveras, Annette; Maunganidze, Nicollette; McDermott, Jason; McGarvey, Peter B.; McGee, John P.; Mieczkowski, Piotr A.; Migliozzi, Simona; Montgomery, Rebecca; Newton, Chelsea J.; Özbek, Umut; Paulovich, Amanda G.; Payne, Samuel H.; Pazardzhikliev, D; Perou, Amy M.; Petralia, Francesca; Petrenko, Lyudmila; Piehowski, Paul; Placantonakis, Dmitris; Polonskaya, Larisa; Пономарева, Е. В.; Potapova, Olga; Qi, Liqun; Qu, Ning; Ramkissoon, Shakti; Reva, Boris; Richey, Shannon; Robinson, Karna; Roche, Nancy; Rodland, Karin D.; Rohrer, Daniel C.; Rykunov, Dmitry; Schadt, Eric E.; Shi, Yan; Shutack, Yvonne; Singh, Shilpi; Skelly, Tara; Smith, Richard V.; Sokoll, Lori J.; Stawicki, Jakub; Stein, Stephen E.; Suh, James; Szopa, Wojciech; Tabor, Dave; Tan, Donghui; Tansil, Darlene; Teo, Guo Ci; Thangudu, Ratna R.; Tognon, Cristina E.; Traer, Elie; Tsang, Shirley; Tyner, Jeffrey W.; Um, Ki Sung; Valley, Dana R.; Vasilev, Lyubomir Valkov; Vatanian, Negin; Velvulou, Uma; Vernon, Michael; Westbrook, Thomas F.; Whiteaker, Jeffrey R.; Wu, Yige; Xu, Ming; Yao, Lijun; Yi, Xinpei; Yu, Fengchao; Zaalishvili, Kakhaber; Zakhartsev, Yuriy; Zelt, Robert; Zhao, Grace; Zhu, Jun

doi:10.1016/j.ccell.2020.12.007

Cited by 237 publications

(201 citation statements)

References 153 publications

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“…In contrast to the high fraction of protein overexpression, only 25% of samples in the TCGA-HNSC cohort were identified to have an active EGFR pathway. A recent phosphoproteomic study in HNSCC has identified that EGFR ligands rather than the receptor are the rate-limiting factor for EGFR pathway activity, offering an explanation for this discordance (33). This could be an explanation for the moderate efficacy of cetuximab in HNSCC (34,35).…”

Section: Discussionmentioning

confidence: 99%

EGFR and PI3K Pathway Activities Might Guide Drug Repurposing in HPV-Negative Head and Neck Cancers

et al. 2021

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While genetic alterations in Epidermal growth factor receptor (EGFR) and PI3K are common in head and neck squamous cell carcinomas (HNSCC), their impact on oncogenic signaling and cancer drug sensitivities remains elusive. To determine their consequences on the transcriptional network, pathway activities of EGFR, PI3K, and 12 additional oncogenic pathways were inferred in 498 HNSCC samples of The Cancer Genome Atlas using PROGENy. More than half of HPV-negative HNSCC showed a pathway activation in EGFR or PI3K. An amplification in EGFR and a mutation in PI3KCA resulted in a significantly higher activity of the respective pathway (p = 0.017 and p = 0.007). Interestingly, both pathway activations could only be explained by genetic alterations in less than 25% of cases indicating additional molecular events involved in the downstream signaling. Suitable in vitro pathway models could be identified in a published drug screen of 45 HPV-negative HNSCC cell lines. An active EGFR pathway was predictive for the response to the PI3K inhibitor buparlisib (p = 6.36E-03) and an inactive EGFR and PI3K pathway was associated with efficacy of the B-cell lymphoma (BCL) inhibitor navitoclax (p = 9.26E-03). In addition, an inactive PI3K pathway correlated with a response to multiple Histone deacetylase inhibitor (HDAC) inhibitors. These findings require validation in preclinical models and clinical studies.

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Section: Discussionmentioning

confidence: 99%

EGFR and PI3K Pathway Activities Might Guide Drug Repurposing in HPV-Negative Head and Neck Cancers

et al. 2021

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“…Proteogenomics (the combination of genomics with proteomics) is also beginning to be utilized to toxicity and resistance to therapies and determine precision oncology strategies. The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) has published several seminal manuscripts on various cancer types including pediatric brain cancer (56)(57)(58)(59)(60). We have found proteogenomics to be useful in identifying key pathways involved in metastatic progression to the brain (61).…”

Section: Future Directionsmentioning

confidence: 99%

Brain Tumor Biobank Development for Precision Medicine: Role of the Neurosurgeon

et al. 2021

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Neuro-oncology biobanks are critical for the implementation of a precision medicine program. In this perspective, we review our first year experience of a brain tumor biobank with integrated next generation sequencing. From our experience, we describe the critical role of the neurosurgeon in diagnosis, research, and precision medicine efforts. In the first year of implementation of the biobank, 117 patients (Female: 62; Male: 55) had 125 brain tumor surgeries. 75% of patients had tumors biobanked, and 16% were of minority race/ethnicity. Tumors biobanked were as follows: diffuse gliomas (45%), brain metastases (29%), meningioma (21%), and other (5%). Among biobanked patients, 100% also had next generation sequencing. Eleven patients qualified for targeted therapy based on identification of actionable gene mutations. One patient with a hereditary cancer predisposition syndrome was also identified. An iterative quality improvement process was implemented to streamline the workflow between the operating room, pathology, and the research laboratory. Dedicated tumor bank personnel in the department of neurosurgery greatly improved standard operating procedure. Intraoperative selection and processing of tumor tissue by the neurosurgeon was integral to increasing success with cell culture assays. Currently, our institutional protocol integrates standard histopathological diagnosis, next generation sequencing, and functional assays on surgical specimens to develop precision medicine protocols for our patients. This perspective reviews the critical role of neurosurgeons in brain tumor biobank implementation and success as well as future directions for enhancing precision medicine efforts.

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“…For HPV-negative head and neck squamous cell carcinoma (Huang et al, 2021), three therapeutically actionable molecular subtypes were identified. The first subtype, high chromosome instability (CIN), showed the worst prognosis.…”

Section: Biological Insights From Proteogenomicsmentioning

confidence: 99%

The next horizon in precision oncology: Proteogenomics to inform cancer diagnosis and treatment

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et al. 2021

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When it comes to precision oncology, proteogenomics may provide better prospects to the clinical characterization of tumors, help make a more accurate diagnosis of cancer, and improve treatment for patients with cancer. This perspective describes the significant contributions of The Cancer Genome Atlas and the Clinical Proteomic Tumor Analysis Consortium to precision oncology and makes the case that proteogenomics needs to be fully integrated into clinical trials and patient care in order for precision oncology to deliver the right cancer treatment to the right patient at the right dose and at the right time. DAWN OF A NEW ERA: MOLECULARLY TARGETED THERAPIES FOR CANCERPrecision oncology has made important contributions to the efficacy of cancer treatment. The use of specific genetic perturbations in a patient's tumor to select cancer therapy began in the ll

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Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma

Cited by 237 publications

References 153 publications

EGFR and PI3K Pathway Activities Might Guide Drug Repurposing in HPV-Negative Head and Neck Cancers

EGFR and PI3K Pathway Activities Might Guide Drug Repurposing in HPV-Negative Head and Neck Cancers

Brain Tumor Biobank Development for Precision Medicine: Role of the Neurosurgeon

The next horizon in precision oncology: Proteogenomics to inform cancer diagnosis and treatment

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