Journal ArticleDOI
Advances in molecular diagnostics and therapeutics in head and neck cancer.
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TLDR
Low-toxicity, tumor-specific targeting therapies for SCCHN will soon be a reality, with many more compounds in the pipeline, and the challenge is to establish assays to determine which patients are most likely to benefit from these agents.Abstract:
Extensive treatment-related morbidities and stagnant survival rates over the past few decades for patients with squamous cell cancer of the head and neck (SCCHN) emphasize the need for novel diagnostics and therapeutics based on the molecular characteristics of the tumor. The development of an early detection test remains largely preliminary. Much attention has recently been given to saliva-based early detection assays that use accepted tumor markers such as p53 and DNA methylation. Most of these studies have focused on feasibility as opposed to prospective clinical trials. To date, early detection saliva assays have failed to yield a high enough sensitivity and specificity for broad population-based screening. The use of saliva as a noninvasive, inexpensive, and accessible diagnostic substrate remains desirable. Unlike SCCHN diagnostics, molecular-targeted therapies for SCCHN will soon be a reality, with many more compounds in the pipeline. The most promising of these drugs target the epidermal growth factor receptor (EGFR), which is known to be overexpressed in squamous cell carcinomas. Cetuximab, a monoclonal EGFR antibody, has shown efficacy in combination with radiotherapy in advanced SCCHN in a recent phase III trial and is currently being petitioned for US Food and Drug Administration approval. Likewise, erlotinib, an EGFR tyrosine kinase inhibitor, has shown favorable results in phase II trials as monotherapy and in combination with chemotherapy. Gefitinib, another EGFR tyrosine kinase inhibitor, has shown efficacy as monotherapy, in combination with chemotherapy, and with chemoradiotherapy. At least two phase III trials of gefitinib in patients with advanced SCCHN are ongoing. Such low-toxicity, tumor-specific targeting strategies will soon be available for patients with head and neck cancer. The challenge is to establish assays to determine which patients are most likely to benefit from these agents.read more
Citations
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Salivary microRNA: Discovery, Characterization, and Clinical Utility for Oral Cancer Detection
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TL;DR: Both whole and supernatant saliva of healthy controls contained dozens of miRNA, and similar to saliva mRNAs, these miRNAs are stable and can be used for oral cancer detection.
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TL;DR: The 'magic bullet' concept of specifically targeting cancer cells at the same time as sparing normal tissues is now proven, as several monoclonal antibodies and targeted small-molecule compounds have been approved for cancer treatment.
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Saliva: diagnostics and therapeutic perspectives.
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TL;DR: The avenue of saliva diagnostics incorporating transcriptomic, proteomic and metabolomic findings will enable us to connect salivary molecular analytes to monitor therapies, therapeutic outcomes, and finally disease progression in cancer.
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Cross-talk between G protein-coupled receptor and epidermal growth factor receptor signaling pathways contributes to growth and invasion of head and neck squamous cell carcinoma.
Sufi M. Thomas,Neil E. Bhola,Qing Zhang,Sarah Contrucci,Abbey L. Wentzel,Maria L. Freilino,William E. Gooding,Jill M. Siegfried,Daniel C. Chan,Jennifer R. Grandis +9 more
TL;DR: G protein-coupled receptors (GPCR) and the epidermal growth factor receptor (EGFR) are often both overexpressed and contribute to the growth of cancers by activating autocrine pathways and combined blockade of both EGFR and GPCRs may be a rational strategy to treat cancers, including HNSCC that shows cross-talk between GPCR and EGFR signaling pathways.
Journal ArticleDOI
Epigenetic profiling reveals etiologically distinct patterns of DNA methylation in head and neck squamous cell carcinoma
Carmen J. Marsit,Brock C. Christensen,E. Andres Houseman,E. Andres Houseman,Margaret R. Karagas,Margaret Wrensch,Ru Fang Yeh,Heather H. Nelson,Joseph I. Wiemels,Shichun Zheng,Marshall R. Posner,Michael D. McClean,John K. Wiencke,Karl T. Kelsey +13 more
TL;DR: It is found that the etiologic heterogeneity of HNSCC is reflected in specific patterns of molecular epigenetic alterations within the tumors and that the DNA methylation profiles may hold clinical promise worthy of further study.
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TL;DR: DNA from 61 unrelated patients with adenomatous polyposis coli (APC) was examined for mutations in three genes located within a 100 kb region deleted in two of the patients, and data have established that DP2.5 is the APC gene.
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