Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type, has often an aggressive course and is poorly responsive to current therapeutic approaches, so that 5-year survival rates for patients diagnosed with advanced disease is lower than 50%. The Epidermal Growth Factor Receptor (EGFR) has emerged as an established oncogene in HNSCC. Indeed, although HNSCCs are a heterogeneous group of cancers which differ for histological, molecular and clinical features, EGFR is overexpressed or mutated in a percentage of cases up to about 90%. Moreover, aberrant expression of the other members of the ErbB receptor family, ErbB2, ErbB3 and ErbB4, has also been reported in variable proportions of HNSCCs. Therefore, an increased expression/activity of one or multiple ErbB receptors is found in the vast majority of patients with HNSCC. While aberrant ErbB signaling has long been known to play a critical role in tumor growth, angiogenesis, invasion, metastatization and resistance to therapy, more recent evidence has revealed its impact on other features of cancer cells’ biology, such as the ability to evade antitumor immunity. In this paper we will review recent findings on how ErbB receptors expression and activity, including that associated with non-canonical signaling mechanisms, impacts on prognosis and therapy of HNSCC.

Molecular docking analysis between anti-apoptosis EGFR and four coumarins, and four carbazole alkaloids: in silico study

“…39 Many preclinical and clinical studies have investigated the therapeutic potential of agents targeting EGFR by inactivating or blocking it with various small molecules, both synthetic and natural compounds. 40,41 In accordance with these findings, our in silico analysis showed that the natural compounds four coumarin compounds (clauslactone E, dentatin, nordentatin, Clausenidin) and four carbazole alkaloid compounds (7hydroxyheptaphylline, clausine E, 2,7-dimethoxy -9H -carbazole -3carbaldehyde, and 2,7 -dimethoxy -9H -carbazole -3 -carboxylic acid) have potential as ligands that inhibit the anti-apoptotic EGFR protein.…”

Evaluation of Co-Inhibition of ErbB Family and PI3K Kinases for HPV-Negative Head and Neck Squamous Cell Carcinoma

“…In addition, HER2 and HER3 are also associated with resistance to EGFR and PI3K inhibitors in cancer [25,26]. These results indicate that targeting the ErbB family kinases could more effectively suppress HNSCC compared to solely using EGFR inhibitors [27,28]. In fact, FDA-approved ErbB family inhibitor, Afatinib, has shown positive results in HNSCC clinical trials and is now listed on the National Comprehensive Cancer Network (NCCN) guidelines as a third-line single agent for HNSCC treatment [28][29][30][31][32].…”

Bisphenol-A in Drinking Water Accelerates Mammary Cancerogenesis and Favors an Immunosuppressive Tumor Microenvironment in BALB–neuT Mice

“…In this context, the different subtypes of ErbB2/ neu -positive breast cancers are very aggressive tumors with a high risk of recurrence and poor clinical outcome. Indeed, sustained ErbB2/ neu signaling stimulates proliferation, inhibits apoptosis, confers chemotherapy resistance, and promotes invasion and metastasis of breast cancer cells [ 38 , 39 , 40 ].…”