EGFR and its respective ligands are overexpressed in various tumors and this over-expression correlates with poor prognosis in selected cancers. In addition to direct activation by EGFR autocrine ligands, the large family of G-protein-coupled receptors (GPCRs) has been reported to transactivate EGFR via both ligand-dependent and independent mechanisms. GPCRs can induce the cleavage of membrane-bound EGFR-ligand precursors or directly activate the juxtamembrane tyrosine kinase domain of EGFR. Due to the heterogenous expression of GPCRs in tumors, this form of receptor crosstalk may contribute to the modest clinical responses to EGFR-targeted therapies observed to date. Studies, so far, have indicated that the signaling mechanisms involved in transactivation are specifically influenced by the activated GPCR and the tumor type in question. The progression of colon, lung, breast, head and neck, prostate and ovarian cancers have all been reported to be mediated, at least in part, by GPCR-EGFR crosstalk. Increased understanding of the specific signaling pathways involved in EGFR transactivation by GPCR will facilitate the identification of new biomarkers for molecular targeting strategies.

Importance of the field Head and neck squamous cell carcinoma (HNSCC) is the eighth leading cause of cancer death worldwide. Despite advances in surgery and chemoradiation therapy, there has been little improvement in survival rates over the past 4 decades. Additionally, surgery and chemoradiotherapy have serious side effects. The development of agents with greater efficacy and tolerability is needed. Areas covered in this review EGFR is the only proven molecular target for HNSCC therapy. Cetuximab, the sole FDA-approved molecular targeted HNSCC therapy, and other potential targeted therapies are being evaluated in preclinical, clinical and post-marketing studies. Here, we review the emerging targets for biological agents in HNSCC and the rationale for their selection. What the reader will gain Key information in the development of new drug targets and the emergence of new biomarkers are discussed. Readers will gain insight regarding the limitations of current therapies, the impact of recently approved targeted therapies and the influence that predictive biomarkers will have on drug development. Take home message The head and neck cancer drug market is rapidly evolving. Coordination between drug and biomarker development efforts may soon yield targeted therapies that can achieve the promise of personalized cancer medicine.

In the process of transferring the miR-182-flox and LSL-miR-182 mice to the Jackson Laboratory, the authors realized that the description of how the LSL-miR-182 mice were generated in the manuscript contained an error. Although the miR-182-flox mice were generated by crossing the mice to a flpO deleter strain to delete the Neo cassette, as was stated in the Methods section, the R26-LSL-miR-182 mice were not crossed to a deleter strain. Instead, the R26-LSL-miR-182 mice that were utilized in this work retained the Neo cassette. Two corrected sentences for the Methods section are below.Chimeric males were mated to WT C57BL/6 females to generate heterozygotes. These mice were subsequently crossed to a flpO deleter strain to excise the frt-Neo-frt cassette to generate miR-182-flox mice.The R26-LSL-miR-182 mice that were utilized in this work retained the Neo cassette.The authors regret the error.