|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
Activation of the PI3K/AKT/mTOR pathway downstream to kinase receptors, such as EGFR, was found in 57-81% of head and neck squamous cell carcinoma (HNSCC), and was eventually associated with a loss of PTEN function. mTOR was shown to modulate cell proliferation, apoptosis, invasion, and angiogenesis.
|
17912526 |
2008 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Activation of the PI3K and epidermal growth factor receptor (EGFR) pathway is able to drive oncogenesis in multiple human cancers, including head and neck squamous cell carcinoma.
|
22065749 |
2011 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
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.
|
24219320 |
2015 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
BYL719 is an α-specific PI3K inhibitor that is synergistic and efficacious when combined with cetuximab, an FDA-approved radiosensitizing agent in the treatment of HNSCC.
|
31678634 |
2020 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
Combined treatment with cetuximab and MM-121 blocked EGFR and HER3 activities and inhibited the PI3K/AKT and ERK signaling pathways and HNSCC cell growth more effectively than each antibody alone.
|
27358485 |
2017 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
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.
|
22037217 |
2012 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
Frequent genetic and biochemical alterations of the PI 3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma.
|
15543611 |
2005 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Hence, we investigated the therapeutic efficacy of inhibiting PI3K with GDC-0032, a PI3K inhibitor with potent activity against p110α, in combination with radiation in HNSCC.
|
26589432 |
2016 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
HER3 targeting potentiates growth suppressive effects of the PI3K inhibitor BYL719 in pre-clinical models of head and neck squamous cell carcinoma.
|
31235758 |
2019 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
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.
|
30858165 |
2019 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
HGF-induced phosphorylation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) pathway substrate p42/p44(erk) and phosphatidylinositol 3'-kinase (PI3K) pathway substrate Akt provided evidence for downstream activation of MEK and PI3K pathways in HNSCC.
|
11479233 |
2001 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
HRAS mutant cells are resistant to PI3K inhibition and our findings suggest the involvement of a signalling intersection of the MAPK and PI3K pathways at the level of ERK-TSC2, leading to persistent mTOR activity. mTOR inhibition alone or in combination with MAPK pathway inhibition may be a promising therapeutic strategy for this subset of HNSCC tumors.
|
30115483 |
2018 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
In present study, we investigated the resistant mechanisms and potential combination therapeutic strategy to overcome adaptive resistance to PI3K inhibitor in HNSCC.
|
28945228 |
2018 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
In the present study, we determined the mutation status in members of the MAPK, PI3K-AKT and JAK-STAT pathways in HNSCC.
|
23670291 |
2013 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this article, we review the genetic alterations reported in the pathway pertinent to HNSCC, various agents in development targeting various mediators of the pathway, results from clinical trials, and remaining challenges in the development of PI3K pathway inhibitors.
|
28108737 |
2017 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this study we investigated the activity of PF-04691502, an orally active ATP-competitive, dual inhibitor of PI3K and mTOR, in combination with a clinically relevant fractionated radiation treatment in two contrasting, well characterized, low passage HNSCC models.
|
28823407 |
2017 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
Increasing evidence indicates that both the phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of Rapamycin (mTOR) and the nuclear factor-kappa B (NF-κB) are constitutively active and contribute to aggressive HNSCC downstream of EGFR.
|
26895469 |
2016 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Likewise, we examined the activation of the PI3K/AKT/mTOR pathway in HNSCC tumors by RPPA.
|
25193510 |
2014 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
Most importantly, one mechanism was found that PF-03084014 alone could activate the PI3K/AKT signalling, the downstream of EGFR signalling, and Erlotinib alone could activate the intracellular domain of Notch1 (NICD), while combined treatment of PF-03084014 and Erlotinib suppressed the HNSCC growth.
|
29232766 |
2018 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
NOTCH1 inhibition or knockout increased <i>NOTCH1</i><sup>WT</sup> HNSCC sensitivity to PI3K/mTOR inhibition.
|
30770351 |
2019 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
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.
|
24941990 |
2014 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
One mechanism by which HPV-associated HNSCC might activate PI3K is increased expression of PIK3CA.
|
17848307 |
2007 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our result suggests that co-targeting of Ephs, TRKs and the c-Kit pathway may be effective at eliminating the PI3K-independent CSC population, thereby providing potential targets for future development of a novel anti-CSC therapeutic approach for HNSCC patients, particularly for patients with PIK3CA amplification.
|
31600013 |
2020 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our results strongly suggest that cotargeting of EGFR and PI3K is synergistic and induces apoptosis of SCCHN cell lines by inhibiting both axes of the AKT-mTOR pathway and translational regulation of antiapoptotic Bcl-2 proteins.
|
28119490 |
2017 |
|
Squamous cell carcinoma of the head and neck
|
0.100 |
Biomarker
|
disease |
BEFREE |
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.
|
24425785 |
2014 |