Genetic profile of head and neck squamous cell carcinoma: clinical implications

Agada, Frank; Patmore, H S; Alhamarneh, Osama; Stafford, Nicholas D.; Greenman, John

doi:10.1017/s0022215108003320

Cited by 20 publications

(17 citation statements)

References 52 publications

(40 reference statements)

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“…In advanced stages, SCC treatment often requires complete excision of tumor using specialized surgical techniques [5]. Unfortunately, the survival rate of SCC patients has not improved significantly over the last couple of decades, even after substantial advances in cancer treatment strategies [6]. …”

Section: Introductionmentioning

confidence: 99%

Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

Khan

Yadav

et al. 2017

Cell Mol Biol Lett

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Squamous cell carcinoma (SCC) is the most common cancer worldwide. The treatment of locally advanced disease generally requires various combinations of radiotherapy, surgery, and systemic therapy. Despite aggressive multimodal treatment, most of the patients relapse. Identification of molecules that sustain cancer cell growth and survival has made molecular targeting a feasible therapeutic strategy. Survivin is a member of the Inhibitor of Apoptosis Protein (IAP) family, which is overexpressed in most of the malignancies including SCC and totally absent in most of the normal tissues. This feature makes survivin an ideal target for cancer therapy. It orchestrates several important mechanisms to support cancer cell survival including inhibition of apoptosis and regulation of cell division. Overexpression of survivin in tumors is also associated with poor prognosis, aggressive tumor behavior, resistance to therapy, and high tumor recurrence. Various strategies have been developed to target survivin expression in cancer cells, and their effects on apoptosis induction and tumor growth attenuation have been demonstrated. In this review, we discuss recent advances in therapeutic potential of survivin in cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

Khan

Yadav

et al. 2017

Cell Mol Biol Lett

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“…1 SCCs, other than those in the skin, commonly metastasize, 2,3 and the survival rates have not improved in decades. A better understanding of the underlying biology of SCCs is just beginning to be elucidated, 4 but would be enhanced by the characterization of their common molecular alterations.…”

Section: Introductionmentioning

confidence: 99%

Squamousness: Next-generation sequencing reveals shared molecular features across squamous tumor types

Schwaederlé

Elkin²,

Tomson³

et al. 2015

Cell Cycle

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Disclosure: An abstract has been accepted for ASCO annual meeting 2015 (Poster session).Keywords: cancer, gene signature, next-generation sequencing, squamous, SCCIn order to gain a better understanding of the underlying biology of squamous cell carcinoma (SCC), we tested the hypothesis that SCC originating from different organs may possess common molecular alterations. SCC samples (N D 361) were examined using clinical-grade targeted next-generation sequencing (NGS). The most frequent SCC tumor types were head and neck, lung, cutaneous, gastrointestinal and gynecologic cancers. The most common gene alterations were TP53 (64.5% of patients), PIK3CA (28.5%), CDKN2A (24.4%), SOX2 (17.7%), and CCND1 (15.8%). By comparing NGS results of our SCC cohort to a non-SCC cohort (N D 277), we found that CDKN2A, SOX2, NOTCH1, TP53, PIK3CA, CCND1, and FBXW7 were significantly more frequently altered, unlike KRAS, which was less frequently altered in SCC specimens (all P < 0.05; multivariable analysis). Therefore, we identified "squamousness" gene signatures (TP53, PIK3CA, CCND1, CDKN2A, SOX2, NOTCH 1, and FBXW7 aberrations, and absence of KRAS alterations) that were significantly more frequent in SCC versus non-SCC histologies. A multivariable co-alteration analysis established 2 SCC subgroups: (i) patients in whom TP53 and cyclin pathway (CDKN2A and CCND1) alterations strongly correlated but in whom PIK3CA aberrations were less frequent; and (ii) patients with PIK3CA alterations in whom TP53 mutations were less frequent (all P 0 .001, multivariable analysis). In conclusion, we identified a set of 8 genes altered with significantly different frequencies when SCC and non-SCC were compared, suggesting the existence of patterns for "squamousness." Targeting the PI3K-AKT-mTOR and/or cyclin pathway components in SCC may be warranted.

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“…It is the most common metastasizing cancer worldwide, and its survival rate has not improved significantly in the past 30 years. 1, 2 Although SCC arises from different organs, SCCs share many phenotypic and molecular characteristics with each other. 3 Further understanding of the common molecular mechanism associated with squamous epithelial homeostasis and progression of SCC will be of great benefit for better prevention and treatment of SCC.…”

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confidence: 99%

Loss of TACSTD2 contributed to squamous cell carcinoma progression through attenuating TAp63-dependent apoptosis

et al. 2014

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Tumor-associated calcium signal transducer 2 (TACSTD2), a calcium signal transducer, is universally expressed in stratified squamous epithelia of many organs, including skin, esophagus and cervix. Although TACSTD2, was reported to be overexpressed in many epithelial tumors, which has increased interest in using it as a molecular target for cancer therapy, the role of TACSTD2 in carcinogenesis of squamous cell carcinoma (SCC) is largely unclear and controversial. To explore the role of TACSTD2, temporal-spatial expression of TACSTD2 was analyzed in both normal and SCC tissues. Our data demonstrate that Tacstd2 expression and membrane localization are tightly associated with stratified epithelial homeostasis, while loss of TACSTD2 was identified in poorly differentiated SCC tissues collected from cervix, esophagus, head and neck. Gradual loss of TACSTD2 was correlated with stepwise progression of SCC. Consistent with these in vivo observations, our data show that inhibition of Tacstd2 expression significantly inhibited chemotherapeutic reagent-induced apoptosis, and TACSTD2 regulated apoptotic gene expression through P63 containing the transactivation domain (TAp63). These findings indicated that loss of TACSTD2 could promote SCC progression and treatment resistance through attenuating chemotherapeutic reagent-induced apoptosis through TAp63, and TACSTD2 could be used as a marker for pathological grading of SCC.

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Genetic profile of head and neck squamous cell carcinoma: clinical implications

Cited by 20 publications

References 52 publications

Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

Squamousness: Next-generation sequencing reveals shared molecular features across squamous tumor types

Loss of TACSTD2 contributed to squamous cell carcinoma progression through attenuating TAp63-dependent apoptosis

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