PI3‐kinase pathway biomarkers in oral cancer and tumor immune cells

Ibrahim, Mohammad; Nunez, María I.; Harun, Nusrat; Lee, John; El‐Naggar, Adel K.; Ferrarotto, Renata; Wistuba, Ignacio I.; Myers, Jeffrey N.; Glisson, Bonnie S.; William, William N.

doi:10.1002/hed.25350

Cited by 6 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients with metastatic melanoma who initially responded to anti-PD-1 alone or in combination with anti-CTLA-4 and then progressed were analyzed, and PTEN-loss was identified in 5 cases in the post-progression biopsy out of 18 intact PTEN expression in pre-treatment biopsies ( 107 ). In surgically treated oral cavity squamous cell carcinomas, PTEN loss in tumor infiltrating immune cells has been associated with worse prognosis ( 108 ). Similarly to PTEN-loss, WNT-β-catenin promotes an immunosuppressive tumor microenvironment that may be responsible for secondary resistance to immunotherapy ( 106 , 109 ).…”

Section: Resistance To Immunotherapiesmentioning

confidence: 99%

Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas

2021

Self Cite

View full text Add to dashboard Cite

Preclinical data suggest that head and neck squamous cell carcinomas (HNSCC) may evade immune surveillance and induce immunosuppression. One mechanism of immune evasion involves the expression of programmed death ligand-1 (PD-L1) in tumor and immune cells, which is, to date, the only biomarker routinely used in clinical practice to select patients with advanced HNSCCs more likely to benefit from anti-PD-1 therapy. Nonetheless, PD-L1 expression alone incompletely captures the degree of sensitivity of HNSCCs to PD-1 inhibitors. Most patients exposed to anti-PD-1 antibodies do not respond to therapy, suggesting the existence of mechanisms of de novo resistance to immunotherapy. Furthermore, patients that initially respond to PD-1 inhibitors will eventually develop acquired resistance to immunotherapy through mechanisms that have not yet been completely elucidated. In this article, we will provide an overview of the immune landscape of HNSCCs. We will briefly describe the clinical activity of inhibitors of the PD-1/PD-L1 axis in this disease, as well as biomarkers of benefit from these agents that have been identified so far. We will review pre-clinical and clinical work in cancers in general, and in HNSCCs specifically, that have characterized the mechanisms of de novo and acquired resistance to immunotherapy. Lastly, we will provide insights into novel strategies under investigation to overcome resistance to immune checkpoint inhibitors.

show abstract

Section: Resistance To Immunotherapiesmentioning

confidence: 99%

Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas

2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Increase in PI3K increases AKT, thereby suggesting a positive correlation between PI3K and ATK. Ibrahim M, et al found that activation of the PI3-kinase pathway in cancer cells was associated with higher risk of recurrence and/or death through activation of p-AKT pathway [13]. Multiple types of tumor malignancies have been identified to activate the PI3K/AKT pathway [14].…”

Section: Discussionmentioning

confidence: 99%

Comparative Evaluation on the Expression of Pi3 Kinase - AKT- mTOR Signalling Molecules in Oral Squamous Cell Carcinoma - A Real Time PCR Based Approach

Umashankar

Jayaraman

Ramani

2021

JPRI

View full text Add to dashboard Cite

Background: Oral squamous cell cancer (OSCC) develops as a result of the accumulation of many genetic mutations that are influenced by genetic predisposition. Upon acquisition of genetic predisposition, the precancerous cells will transform into malignant cells culminating into carcinomas. Advances in genetic research over the past few decades have rendered early detection possible. Aim: To compare the gene expression of Pi3 Kinase, AKT and mTOR in OSCC and to correlate the expression levels of these molecules with the survival in OSCC patients. Also to understand the role of Pi3 Kinase pathway in OSCC progression thereby attempting targeted therapy in OSCC patients. Materials and Methods: 10 OSCC samples as well as normal healthy samples were collected and RNA isolation was done using RNA easy kit from Qiagen (Valencia, CA), and then subjected to cDNA synthesis using Human TGF-β1, Human GSK-3β and Human Pi3 kinase primers. Real time PCR was performed using gene specific primers at 40 cycles. The results were retrieved, tabulated and analyzed. Results: The current research results revealed that there were up regulation of mRNA expression in The PI3K/AKT/mTOR in OSCC patients than in healthy individuals. On comparison, mTOR showed highest mRNA expression levels than AKT and PI3K. Conclusion: Overexpression of Pi3 kinase, AKT, mTOR plays a crucial role in progression of oral cancer and targeting Pi3 kinase/mTOR pathways could be a novel and targeted approach for OSCC.

show abstract

“…As a key protein in the Akt/PI3K signaling pathway, p-AKT (phosphorylated Akt) may be an important link between oxidative stress and cancer. Therefore, we researched a large number of studies and found that overexpression of p-AKT is firmly related to the prognosis of various hematologic tumors and solid tumors, such as non-small cell lung cancer (NSCLC) (5)(6)(7)(8), gastric cancer (GC) (9)(10)(11)(12), squamous cell carcinoma (SCC) (13)(14)(15)(16), hepatocellular carcinoma (HCC) (17)(18)(19), ovarian cancer (OC) (20,21), diffuse large B-cell lymphoma (DLBCL) (22,23), urothelial carcinoma (UC) (24,25), nasopharyngeal carcinoma (NC) (26), pediatric Burkitt lymphoma (PBL) (27), hairy cell leukemia (HCL) (28), peripheral T-cell lymphoma (PTCL) (29), anaplastic large cell lymphoma (ALCL) (30), breast cancer (BC) (31), endometrial carcinoma (EC) (32), and pancreatic cancer (PC) (33).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Role of the Activated p-AKT Molecule in Various Hematologic Malignancies and Solid Tumors: A Meta-Analysis

et al. 2020

View full text Add to dashboard Cite

Cancer is one of the main causes of human death worldwide. Recently, many studies have firmly established the causal relationship between oxidative stress and cancer initiation and progression. As a key protein in PI3K/Akt signaling pathway, p-AKT (phosphorylated Akt) participates in the process of oxidative stress and plays a prognostic role in various hematologic tumors and solid tumors. We conducted a comprehensive search of the PubMed, Embase and Cochrane libraries to identify studies published in the past decade involving cancer patients expressing p-AKT that reported overall survival (OS) during follow-up. In this study, 6,128 patients in total were evaluated from 29 enrolled articles, and we concluded that overexpression of p-AKT was closely related to worse OS in cancer patients with a hazard ratio (HR) of 2.33 (95% CI: 1.67–4.00). Furthermore, we conducted a subgroup analysis, and the results indicated that overexpression of p-AKT was associated with worse OS in hematological tumor (HR: 1.64, 95% CI: 1.41–1.92), and solid tumor (HR: 2.44, 95% CI: 1.61–5.26). High expression of p-AKT is related to poor prognosis of various hematologic tumors and solid tumors.

show abstract

PI3‐kinase pathway biomarkers in oral cancer and tumor immune cells

Cited by 6 publications

References 34 publications

Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas

Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas

Comparative Evaluation on the Expression of Pi3 Kinase - AKT- mTOR Signalling Molecules in Oral Squamous Cell Carcinoma - A Real Time PCR Based Approach

Prognostic Role of the Activated p-AKT Molecule in Various Hematologic Malignancies and Solid Tumors: A Meta-Analysis

Contact Info

Product

Resources

About