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  • American Association for Cancer Research (AACR)  (2)
  • Myers, Jeffrey N.  (2)
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  • American Association for Cancer Research (AACR)  (2)
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  • 1
    Online Resource
    Online Resource
    Abstract 3441: Proteomic profiling identifies PTK2/FAK as a targetable marker of radioresistance in head and neck cancer
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 3441-3441
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 3441-3441
    Abstract: One of the primary treatments for head and neck squamous cell carcinoma (HNSCC) is radiotherapy. Despite decades of study, few if any targetable biomarkers for resistance to this modality. To systematically evaluate resistance to radiotherapy in HNSCC, we evaluated 50 HNSCC cell lines using reverse phase protein array (RPPA). Utilizing this method we identified 11 protein markers with altered expression in radioresistant HNSCC cell lines (FDR 1%), including PTK2/FAK. Both PTK2/Fak gene expression and copy number were highly correlated to PTK2/Fak protein expression and both were associated with radioresistance in these cell lines. Additionally, in clinical samples from the TCGA, PTK2/Fak copy number was highly associated with gene expression, with high expression levels in HNSCC tumors. To validate the association between PTK2/Fak and clinical radioresistance in HNSCC, we examined PTK2/FAK copy number in two separate cohorts of HNSCC patients treated uniformly with radiotherapy (n = 39 and n = 44). In both cohorts, PTK2/Fak amplification was associated with treatment failure following radiotherapy (p = 0.04 and p = 0.03 respectively and p = 0.004 for the combined population). Additionally, in a separate cohort of HNSCC patients treated with radiotherapy, high levels of PTK2/Fak gene expression were associated with failure following radiotherapy (p = 0.02). Additionally, in vitro pharmacologic inhibition of PTK2/FAK function led to radiosensitization in multiple HNSCC cell lines, primarily via induction of G2/M arrest, with minimal apoptosis observed. Taken together, these data identify a validated, targetable biomarker of radioresistance in HNSCC. Citation Format: Heath D. Skinner, Uma Giri, John S. Yordy, Michael D. Story, Jing Wang, Lauren A. Byers, Michelle D. Williams, Adel K. El-Naggar, Sang H. Woo, Liang P. Yang, You Fan, Curtis R. Pickering, Jeffrey N. Myers,, John V. Heymach. Proteomic profiling identifies PTK2/FAK as a targetable marker of radioresistance in head and neck cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3441. doi:10.1158/1538-7445.AM2015-3441
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-3441
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 7 ( 2015-04-01), p. 1527-1536
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 7 ( 2015-04-01), p. 1527-1536
    Abstract: TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations. Cancer Res; 75(7); 1527–36. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-14-2735
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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