scholarly journals Clinical Development of Molecular Targeted Therapy in Head and Neck Squamous Cell Carcinoma

2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Paul Gougis ◽  
Camille Moreau Bachelard ◽  
Maud Kamal ◽  
Hui K Gan ◽  
Edith Borcoman ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cancer Biology ◽  
Molecular Targeted Therapy ◽  
Locally Advanced ◽  
Clinical Development ◽  
Neck Squamous Cell Carcinoma

Abstract A better understanding of cancer biology has led to the development of molecular targeted therapy, which has dramatically improved the outcome of some cancer patients, especially when a biomarker of efficacy has been used for patients’ selection. In head and neck oncology, cetuximab that targets epidermal growth factor receptor is the only targeted therapy that demonstrated a survival benefit, both in the recurrent and in the locally advanced settings, yet without prior patients’ selection. We herein review the clinical development of targeted therapy in head and neck squamous cell carcinoma in light of the molecular landscape and give insights in on how innovative clinical trial designs may speed up biomarker discovery and deployment of new molecular targeted therapies. Given the recent approval of immune checkpoint inhibitors targeting programmed cell death-1 in head and neck squamous cell carcinoma, it remains to be determined how targeted therapy will be incorporated into a global drug development strategy that will inevitably incorporate immunotherapy.

scholarly journals Recent Research on Combination of Radiotherapy with Targeted Therapy or Immunotherapy in Head and Neck Squamous Cell Carcinoma: A Review for Radiation Oncologists

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5716
Author(s):  
Daniel Tao Xing ◽  
Richard Khor ◽  
Hui Gan ◽  
Morikatsu Wada ◽  
Tai Ermongkonchai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Neck Squamous Cell Carcinoma ◽  
Oropharyngeal Carcinoma ◽  
Concurrent Radiotherapy

Radiotherapy plays an important role of managing head and neck squamous cell carcinoma (HNSCC). Concurrent radiotherapy with radiosensitizing cisplastin chemotherapy is the standard of care (SOC) for non-operable locally advanced HNSCC. Cetuximab, a monoclonal antibody of epidermal growth factor receptor, was the most extensively studied targeted therapy as a chemo-sparing agent that was used concurrently with radiotherapy. Immunotherapy is used in the treatment of metastatic HNSCC. There is evidence to support the synergistic effect when combining radiotherapy with immunotherapy to potentiate anti-tumor immune response. There has been increasing interest to incorporate immune checkpoint inhibitor (ICI) with radiotherapy in the curative setting for HNSCC. In this review, we discuss the latest evidence that supports concurrent radiotherapy with cisplatin which remains the SOC for locally advanced HNSCC (LA-HNSCC). Cetuximab is suitable for patients who are not fit for cisplatin. We then summarize the clinical trials that incorporate ICI with radiotherapy for LA-HNSCC in concurrent, neoadjuvant, and adjuvant settings. We also discuss the potential of combining immunotherapy with radiotherapy as a treatment de-escalating strategy in HPV-associated oropharyngeal carcinoma. Finally, the pre-clinical and clinical evidence of the abscopal effect when combining stereotactic body radiotherapy with ICIs is presented.

Different Aspects of Head and Neck Squamous Cell Carcinoma: Cancer Stem Cells, Their Niche and Targeted Therapy

2020 ◽  
Vol 15 ◽  
Author(s):  
Meriç Bilgiç Küçükgüven ◽  
Betül Çelebi-Saltik
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Targeted Therapy ◽  
Cancer Stem Cells ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Crucial Role ◽  
Tumor Therapy ◽  
Neck Squamous Cell Carcinoma

: Head and Neck Squamous Cell Carcinoma (HNSCC) is categorized as the sixth most common cancer worldwide, with an incidence of more than 830,000 cases per year and a mortality rate of 50%. Tobacco use, alcohol consumption, and Human Papillomavirus infection are the prominent risks for HNSCC. Despite significant developments in the treatment of HNSCC, a high rate of recurrences makes the clinical situation worse and results in poor survival rates. Recent perspectives demonstrate that whereas epithelial transformation plays a crucial role in cancer development, tumor surrounding microenvironment takes part in progression of cancer as well. Cancer Stem Cells (CSCs), which harbor unlimited self-renewal capacity, have a crucial role in the growth of HNSCC and this cell population is responsible for tumor recurrence unless eliminated by targeted therapy. CSCs are not only a promising target for tumor therapy, but also a crucial biomarker to determine the patients at high risk for undetermined results and disease development. Just as the bone marrow which is the niche of hematopoietic and mesenchymal stem cells, is important for stem cells maintenance. Similarly, the concept of microenvironment is also important for the maintenance of CSCs. Apart from the cell-cell interactions, there are many parameters in the cancer microenvironment that affect the development of cancer, such as extracellular regulation, vascularization, microbial flora, pH and oxygenation. The purpose of this review is to introduce HNSCC, explain the role of CSCs and their microenvironment and refer to the conventional and novel targeted therapy for HNSCC and CSCs.

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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