scholarly journals EGFR Monoclonal Antibodies in the Treatment of Squamous Cell Carcinoma of the Head and Neck: A View beyond Cetuximab

2012 ◽  
Vol 2012 ◽  
pp. 1-10
Author(s):  
Scott A. Kono ◽  
Missak Haigentz ◽  
Sue S. Yom ◽  
Nabil Saba
Keyword(s):  
Squamous Cell Carcinoma ◽  
Monoclonal Antibodies ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Metastatic Disease ◽  
Squamous Cell ◽  
Locally Advanced ◽  
The United States ◽  
Primary Therapy ◽  
Metastatic Setting

Squamous cell carcinoma of the head and neck (SCCHN) is a prevalent disease both in the United States and worldwide with an overall poor prognosis, in part due to limited activity of existing therapy. Primary therapy is largely dictated by the anatomical origin of the cancer and whether distant disease is present. Many patients with localized disease are treated with chemoradiotherapy, either in the definitive or adjuvant setting, and those with metastatic disease are treated with palliative chemotherapy. The chemotherapy used in SCCHN can be toxic, whether given with radiation or alone. The epidermal growth factor receptor (EGFR) is highly expressed in SCCHN and serves as a logical therapeutic target. EGFR-directed monoclonal antibodies (MoAbs) have higher activity in SCCHN than small molecule tyrosine kinase inhibitors. Cetuximab, a widely studied EGFR MoAb, is FDA approved in the metastatic setting, as well as with radiation for locally advanced disease. Despite improvements in survival when cetuximab is incorporated with chemotherapy for metastatic disease, the prognosis of patients remains poor. Novel EGFR MoAbs are being developed with the goal of improving efficacy and tolerability. This paper will summarize the use of EGFR-directed MoAbs in treating SCCHN with a focus on novel agents being tested.

scholarly journals Recent Advances and Future Directions in Clinical Management of Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 338
Author(s):  
Jameel Muzaffar ◽  
Shahla Bari ◽  
Kedar Kirtane ◽  
Christine H. Chung
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Multidisciplinary Treatment ◽  
Locally Advanced ◽  
The United States ◽  
Neck Squamous Cell Carcinoma ◽  
Treatment Modalities ◽  
Radiation Technology

Head and neck squamous cell carcinoma (HNSCC) is the most common cancer arising in the head and neck region. The most common risk factors are smoking, excessive drinking, and human papillomavirus (HPV) infection. While the overall incidence of smoking is decreasing, the incidence of HPV-related HNSCC is increasing in the United States and Western Europe, which led to a shift in understanding of the pathophysiology, treatment, and prognosis of this disease. The outcomes for non-metastatic HNSCC remains very encouraging and continues to improve. Advances in radiation technology and techniques, better organ preserving surgical options, and multidisciplinary treatment modalities have improved cure rates for locally advanced HNSCC patients. The treatment of metastatic disease, however, remains an area of need. The advancement of immune checkpoint inhibitors has provided significantly better outcomes, but only a small proportion of patients obtain benefits. Most recurrent and/or metastatic HNSCC patients continue to have poor survival. This has led to the vigorous investigation of new biomarkers and biomarker-based therapies. Novel therapeutic options including adaptive cellular therapy and therapeutic vaccines are also on the horizon. In this review, we highlight the latest advances in the field of HNSCC and the future direction of research.

scholarly journals Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3038
Author(s):  
Mickaël Burgy ◽  
Aude Jehl ◽  
Ombline Conrad ◽  
Sophie Foppolo ◽  
Véronique Bruban ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cell Cycle Progression ◽  
Locally Advanced ◽  
Treatment Resistance ◽  
Neck Squamous Cell Carcinoma ◽  
Hnscc Cell

The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment. In clinicopathological practice, it is difficult to assign patients to classes of risk because no reliable biomarkers are available to predict the outcome of HPV-unrelated HNSCC. In the present study, we investigated the role of Caveolin-1 (Cav1) in the sensitivity of HNSCC cell lines to CTX-radiotherapy that might predict HNSCC relapse. Ctrl- and Cav-1-overexpressing HNSCC cell lines were exposed to solvent, CTX, or irradiation, or exposed to CTX before irradiation. Growth, clonogenicity, cell cycle progression, apoptosis, metabolism and signaling pathways were analyzed. Cav1 expression was analyzed in 173 tumor samples and correlated to locoregional recurrence and overall survival. We showed that Cav1-overexpressing cells demonstrate better survival capacities and remain proliferative and motile when exposed to CTX-radiotherapy. Resistance is mediated by the Cav1/EREG/YAP axis. Patients whose tumors overexpressed Cav1 experienced regional recurrence a few years after adjuvant radiotherapy ± chemotherapy. Together, our observations suggest that a high expression of Cav1 might be predictive of locoregional relapse of LA-HNSCC.

scholarly journals Disulfiram Acts as a Potent Radio-Chemo Sensitizer in Head and Neck Squamous Cell Carcinoma Cell Lines and Transplanted Xenografts

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 517
Author(s):  
Wenhao Yao ◽  
Xu Qian ◽  
Sebastian Ochsenreither ◽  
Ferrone Soldano ◽  
Albert B. DeLeo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Colony Formation ◽  
Therapeutic Potential ◽  
Synergistic Effects ◽  
Locally Advanced ◽  
Neck Squamous Cell Carcinoma ◽  
Tumor Xenograft

The poor prognosis of locally advanced and metastatic head and neck squamous cell carcinoma (HNSCC) is primarily mediated by the functional properties of cancer stem cells (CSCs) and resistance to chemoradiotherapy. We investigated whether the aldehyde dehydrogenase (ALDH) inhibitor disulfiram (DSF) can enhance the sensitivity of therapy. Cell viability was assessed by the 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and apoptosis assays, and the cell cycle and reactive oxygen species (ROS) levels were evaluated by fluorescence-activated cell sorting (FACS). The radio-sensitizing effect was measured by a colony formation assay. The synergistic effects were calculated by combination index (CI) analyses. The DSF and DSF/Cu2+ inhibited the cell proliferation (inhibitory concentration 50 (IC50) of DSF and DSF/Cu2+ were 13.96 μM and 0.24 μM). DSF and cisplatin displayed a synergistic effect (CI values were <1). DSF or DSF/Cu2+ abolished the cisplatin-induced G2/M arrest (from 52.9% to 40.7% and 41.1%), and combining irradiation (IR) with DSF or DSF/Cu2+ reduced the colony formation and attenuated the G2/M arrest (from 53.6% to 40.2% and 41.9%). The combination of cisplatin, DSF or DSF/Cu2+, and IR enhanced the radio-chemo sensitivity by inducing apoptosis (42.04% and 32.21%) and ROS activity (46.3% and 37.4%). DSF and DSF/Cu2+ enhanced the sensitivity of HNSCC to cisplatin and IR. Confirming the initial data from patient-derived tumor xenograft (PDX) supported a strong rationale to repurpose DSF as a radio-chemosensitizer and to assess its therapeutic potential in a clinical setting.

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