Tissue biopsies of 25 consecutive cases of HNSCC were tested for activating PIK3CA mutations at three mutational hotspots by real-time polymerase chain reaction.
We identified frequent PIK3CA mutations in patients with high-risk HNSCC confined predominantly to the oropharyngeal and sinonasal subsites; for the first time, mutation in AKT1 has been identified in HNSCC.
Screening of PI3K pathway mutation and inflammatory cytokine expression may help identify which R/M-SCCHN patients are likely to gain benefit from dacomitinib.
The poor prognostic value of GOF <i>TP53</i> variants and mTOR pathway upregulation was confirmed in the TCGA SCCHN cohort.<b>Conclusions:</b> Our study demonstrates a link of intratumoral heterogeneity and clonal evolution as important mechanisms of drug resistance in SCCHN and establishes mutant GOF <i>TP53</i> variants and the PI3K/mTOR pathway as molecular targets for treatment optimization.<i></i>.
Blood samples from treatment naïve HNSCC patients (<i>n</i> = 29) were interrogated for a commonly mutated PIK3CA hotspot mutation using low cost allele-specific Plex-PCR<sup>TM</sup> technology.
In conclusion, this study demonstrates that P120CTN downregulation and PIK3CA mutations promote MMP1-driven invasion, providing a potential novel target for limiting metastasis in HNSCC.<b>Implications:</b> Because of its role in invasion, MMP1 represents a novel, potential target for limiting metastasis in a subset of HNSCCs with P120CTN downregulation and <i>PIK3CA</i> mutations.<i></i>.
PIK3CA showed a uniquely high rate of mutations within the helicase domain, and FGFR3 contained a predominance of hotspot S249C alterations that were not found in HPV- HNSCC.
Conditional activation of the PI3K/Akt pathway due to Pten deletion in the mouse head and neck epithelia gives rise to hyperproliferation, but only a few lesions progress to HNSCC.
Furthermore, although FGFR3-TACC3 fusion proteins promote resistance of additional EGFR-dependent HNSCC and lung cancer cell lines to EGFR blockade, they are unable to compensate for inhibition of PI3K signaling in PIK3CA-mutant HNSCC cell lines.
Pharmacologic profiling of eight anticancer agents in six HNSCC cell lines suggested that PIK3CA mutation may serve as a predictive biomarker for the drugs targeting the EGFR/PI3K pathway.
As such, current research aimed at elucidating the interactions between PI3K/Akt/mTOR and other important signaling pathways which may drive resistance in HNSCC, such as p53, NF-κB, and MAPK, has become a prominent focus toward better understanding how to most effectively treat HNSCC.
Here, we examined the responses of a large panel of patient-derived HNSCC cell lines to various combinations of PI3K and EGFR inhibitors, including EGFR agents with varying specificity and mechanistic characteristics.
Novel therapies under investigation in HNSCC include antibody and small molecule inhibitors of EGF receptor and its family members, PI3K inhibitors, antiangiogenic agents, immunotherapies and agents interacting with early developmental pathways such as Hedgehog.
Emphasis is placed on the therapeutic implications of genes frequently altered in HNSCCs (i.e., TP53, PIK3CA, and NOTCH1) and their corresponding pathways, with a particular focus on recent findings of Notch signaling pathway activation in HNSCC.
Benign tonsils infected with high-risk HPV harbored mutations in EP300, NF1, PIK3CA, and RB1 which are considered relevant in the development of HPV-associated head and neck squamous cell carcinoma (SCC).
This study assessed the maximum tolerated dose (MTD) of the PI3K inhibitor buparlisib given concurrently with cetuximab in recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
The importance of PIK3CA alterations in squamous cell carcinoma of the head and neck (HNSCC) has raised interest in exploring agents targeting PI3K, the product of PIK3CA.