Exploiting the head and neck cancer oncogenome: widespread PI3K-mTOR pathway alterations and novel molecular targets.

نویسندگان

  • Ramiro Iglesias-Bartolome
  • Daniel Martin
  • J Silvio Gutkind
چکیده

SUMMARY Two studies published in this issue of Cancer Discovery describe the emerging mutational landscape of head and neck squamous cell carcinomas (HNSCC) and their genomic and epigenetic alterations, thus identifying novel actionable cancer drivers and predictive biomarkers for targeted therapies. Most genomic alterations in HNSCC converge in a handful of molecular pathways, resulting in cell-cycle deregulation, genomic instability, cell differentiation defects, and persistent mitogenic signaling, the latter involving aberrant phosphoinositide 3-kinase (PI3K)/mTOR pathway activation, thereby rendering HNSCC responsive to PI3K/mTOR inhibitors. Cancer Discov; 3(7); 722-5. ©2013 AACR.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The head and neck cancer cell oncogenome: a platform for the development of precision molecular therapies

The recent elucidation of the genomic landscape of head and neck squamous cell carcinoma (HNSCC) has provided a unique opportunity to develop selective cancer treatment options. These efforts will require the establishment of relevant HNSCC models for preclinical testing. Here, we performed full exome and transcriptome sequencing of a large panel of HNSCC-derived cells from different anatomical...

متن کامل

Companion Diagnostics and Cancer Biomarkers A Comprehensive Evaluation of Biomarkers Predictive of Response to PI3K Inhibitors and of Resistance Mechanisms in Head and Neck Squamous Cell Carcinoma

The PI3K/AKT/mTOR pathway is frequently activated in head and neck squamous cell carcinoma (HNSCC), but pathway inhibition has variable efficacy. Identification of predictive biomarkers and mechanisms of resistancewould allow selection of patientsmost likely to respond andnovel therapeutic combinations. The purpose of this study was to extend recent discoveries regarding the PI3K/AKT/mTOR pathw...

متن کامل

The determinants of head and neck cancer: Unmasking the PI3K pathway mutations.

Studies attempting to identify and understand the function of mutated genes and deregulated molecular pathways in cancer have been ongoing for many years. The PI3K-PTEN-mTOR signaling pathway is one of the most frequently deregulated pathways in cancer. PIK3CA mutations are found 11%-33% of head and neck cancer (HNC). The hotspot mutation sites for PIK3CA are E542K, E545K and H1047R/L. The PTEN...

متن کامل

The Role of Mammalian Target of Rapamycine Signaling Pathway in Central Nervous System Cancers: A Review

Mammalian mechanistic target of rapamycine (mTOR) is a conserved serine/threonine kinase in the cellular PI3K/Akt/mTOR signaling pathway. This pathway is modified by cellular alterations such as level of energy, growth factors, stresses, as well as the increased environmental level of cancerous cytokines. In general, increase of this kinase protein function is seen in various types of cancers, ...

متن کامل

A comprehensive evaluation of biomarkers predictive of response to PI3K inhibitors and of resistance mechanisms in head and neck squamous cell carcinoma.

The PI3K/AKT/mTOR pathway is frequently activated in head and neck squamous cell carcinoma (HNSCC), but pathway inhibition has variable efficacy. Identification of predictive biomarkers and mechanisms of resistance would allow selection of patients most likely to respond and novel therapeutic combinations. The purpose of this study was to extend recent discoveries regarding the PI3K/AKT/mTOR pa...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Cancer discovery

دوره 3 7  شماره 

صفحات  -

تاریخ انتشار 2013