The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Frequent Mutation of the PI3K Pathway in Head and Neck Cancer Defines Predictive Biomarkers
Open accessAbstract
Genomic findings underscore the heterogeneity of head and neck squamous cell carcinoma (HNSCC). Identification of mutations that predict therapeutic response would be a major advance. We determined the mutationally altered, targetable mitogenic pathways in a large HNSCC cohort. Analysis of whole-exome sequencing data from 151 tumors revealed the phosphoinositide 3-kinase (PI3K) pathway to be the most frequently mutated oncogenic pathway (30.5%). PI3K pathway–mutated HNSCC tumors harbored a significantly higher rate of mutations in known cancer genes. In a subset of human papillomavirus-positive tumors, PIK3CA or PIK3R1 was the only mutated cancer gene. Strikingly, all tumors with concurrent mutation of multiple PI3K pathway genes were advanced (stage IV), implicating concerted PI3K pathway aberrations in HNSCC progression. Patient-derived tumorgrafts with canonical and noncanonical PIK3CA mutations were sensitive to an mTOR/PI3K inhibitor (BEZ-235), in contrast to PIK3CA–wild-type tumorgrafts. These results suggest that PI3K pathway mutations may serve as predictive biomarkers for treatment selection. Significance: Treatment options for HNSCC are limited, in part, because of an incomplete understanding of the targetable mutations that “drive” tumor growth. Here, we define a subgroup of HNSCC harboring activating mutations of genes in the PI3K pathway where targeting the pathway shows antitumor efficacy. These results suggest that PI3K pathway mutation assessment may be used to guide HNSCC therapy. Cancer Discov; 3(7); 761–9. ©2013 AACR. See related commentary by Iglesias-Bartolome et al., p. 722 This article is highlighted in the In This Issue feature, p. 705
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Self-citationLi, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785
The PIK3CA gene is mutated with high frequency in human breast cancers
Bachman, K. E., Argani, P., Samuels, Y., Silliman, N., Ptak, J., Szabo, S., Konishi, H., Karakas, B., Blair, B. G., Lin, C., et al. (2004) · Cancer Biology & Therapy · doi:10.4161/cbt.3.8.994 · Cited by 665
Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins
Rozenblatt-Rosen, O., Deo, R. C., Padi, M., Adelmant, G., Calderwood, M. A., Rolland, T., Grace, M., Dricot, A., Askenazi, M., Tavares, M., et al. (2012) · Nature · doi:10.1038/nature11288 · Cited by 378
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Seiwert, T. Y., Zuo, Z., Keck, M. K., Khattri, A., Pedamallu, C. S., Stricker, T., Brown, C., Pugh, T. J., Stojanov, P., Cho, J., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3310 · Cited by 657
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Metadata
- Authors
- Lui, V. W. Y., Hedberg, M. L., Li, H., Vangara, B. S., Pendleton, K., Zeng, Y., Lu, Y., Zhang, Q., Du, Y., Gilbert, B. R., Freilino, M., Sauerwein, S., Peyser, N. D., Xiao, D., Diergaarde, B., Wang, L., Chiosea, S., Seethala, R., Johnson, J. T., Kim, S., Duvvuri, U., Ferris, R. L., Romkes, M., Nukui, T., Kwok-Shing Ng, P., Garraway, L. A., Hammerman, P. S., Mills, G. B., & Grandis, J. R.
- Venue
- Cancer Discovery
- Published
- 2013-07-01
- Volume
- 3
- Issue
- 7
- Pages
- 761-769
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2122357705
- Cited by
- 589
- References
- 5
- FWCI
- 27.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Lui, V. W. Y., Hedberg, M. L., Li, H., Vangara, B. S., Pendleton, K., Zeng, Y., Lu, Y., Zhang, Q., Du, Y., Gilbert, B. R., Freilino, M., Sauerwein, S., Peyser, N. D., Xiao, D., Diergaarde, B., Wang, L., Chiosea, S., Seethala, R., Johnson, J. T., . . . Grandis, J. R. (2013). Frequent Mutation of the PI3K Pathway in Head and Neck Cancer Defines Predictive Biomarkers. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-13-0103
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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