Systemic therapy for head and neck squamous cell carcinoma: Historical perspectives and recent breakthroughs

Blasco, Michael A.; Svider, Peter F.; Raza, Syed Mohsin; Jacobs, John R.; Folbe, Adam J.; Saraf, Pankhoori; Eloy, Jean Anderson; Baredes, Soly; Fribley, Andrew M.

doi:10.1002/lary.26629

Cited by 28 publications

(17 citation statements)

References 29 publications

(59 reference statements)

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“…One approach in targeted therapy of HNSCC is the use of the EGFR inhibitor cetuximab, although a predictive biomarker for resistance is not available . An up‐regulation of the HhP – in particular GLI expression – has been suggested as one acquired resistance mechanism to anti‐EGFR therapy .…”

Section: Discussionmentioning

confidence: 99%

“…19 One approach in targeted therapy of HNSCC is the use of the EGFR inhibitor cetuximab, although a predictive biomarker for resistance is not available. 20 An up-regulation of the HhPin particular GLI expressionhas been suggested as one acquired resistance mechanism to anti-EGFR therapy. 21 Although we did not test for EGFR in our cohort, it would be of clinical interest if patients with tumour that positively stained for SMO would profit from vismodegib monotherapy or in combination with anti-EGFR therapy.…”

Section: Discussionmentioning

confidence: 99%

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Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

et al. 2019

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AimsBecause the hedgehog signalling pathway plays a major role in many types of cancer and can nowadays be targeted by specific compounds, we aimed to investigate the role of this pathway in squamous cell carcinoma of the head and neck.Methods and resultsNinety‐eight treatment‐naive head and neck cancer specimens were immunohistologically stained for SMO, GLI‐1, p53 and p16 expression and correlated with clinicopathological factors. Immunoreactivity for SMO and GLI‐1 was found in 20 (20.4%) and 52 (53.1%) cases of tumours, respectively. SMO expression correlated with GLI‐1 expression (ρ = 0.258, P = 0.010) in univariate and multivariate analysis (P = 0.007, t = 2.81). In univariate analysis, high SMO expression was associated with shorter overall survival (HR = 0.56; 95% CI = 0.32–0.98; P = 0.044) and disease‐free survival (HR = 0.53; 95% CI = 0.30–0.95; P = 0.034). In multivariate cox regression analysis SMO expression showed a trend towards an independent predictor for shorter overall survival (HR = 0.57; 95% CI = 0.30–1.05; P = 0.072) and disease‐free survival (HR = 0.53; 95% CI = 0.28–1.02; P = 0.056). In head and neck cancer patients with low tumour p16 expression, SMO expression was an independent factor for overall survival (HR = 0.49; 95% CI = 0.24–0.98; P = 0.043) and disease‐free survival (HR = 0.45; 95% CI = 0.22‐0.96; P = 0.037).ConclusionAlthough it needs to be confirmed in larger cohorts, our results suggest that targeting SMO might be a potentially therapeutic option in patients with head and neck cancer. In line, molecular pathological analyses including mutation analysis in the hedgehog pathway might point to additional therapeutic leads.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

et al. 2019

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“…3,7À11 The timeframe of this analysis preceded recent approvals of immunotherapies for use in this patient population, but earlier-developed agents are likely to continue to play a role. 25 The analysis adds to limited clinical-practice data that are focused on patients with difficult-to-treat HNC and helps to lay the groundwork for the evaluation of new and emerging immuno-oncology therapies in these patients.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness Outcomes in Patients With Recurrent or Refractory Head and Neck Cancers: Retrospective Analysis of Data From a Community Oncology Database

Fisher

Fernandes

Olufade

et al. 2018

Clinical Therapeutics

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“…Monoclonal antibody treatment is one of the approaches expected to afford improved care. Cetuximab and Nivolumab have been approved for HNSCC treatment by the Food and Drug Administration (FDA) [5,6]. However, the antitumor effects of antibodies under the aegis of antibody dependent cellular cytotoxicity (ADCC) have proven to be inadequate for solid tumors.…”

Section: Introductionmentioning

confidence: 99%

Saponin Facilitates Anti-Robo1 Immunotoxin Cytotoxic Effects on Maxillary Sinus Squamous Cell Carcinoma

Komatsu

Ohashi

et al. 2020

Journal of Oncology

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Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. The standard treatment of surgery, chemotherapy, and radiotherapy can result in long-term complications which lower the patient’s quality of life, such as eating disorders, speech problems, and disfiguring or otherwise untoward cosmetic issues. Antibody therapy against cancer-specific antigens is advantageous in terms of its lesser side effects achieved by its greater specificity, though the antitumor activity is still usually not enough to obtain a complete cure. Robo1, an axon guidance receptor, has received considerable attention as a possible drug target in various cancers. We have shown previously the enhanced cytotoxic effects of saporin-conjugated anti-Robo1 immunotoxin (IT-Robo1) on the HNSCC cell line HSQ-89 in combination with a photochemical internalization technique. Considering the light source, which has only limited tissue penetrance, we examined the drug internalization effect of saponin. Treatment with saponin facilitated significant cytotoxic effects of IT-Robo1 on HSQ-89 cells. Saponin exerts its own nonspecific cytotoxicity, which may cover the actual extent of the internalization effect. We thus examined whether a flashed treatment with saponin exerted a significant specific cytotoxic effect on cancer cells. The combination of an immunotoxin with saponin also exhibited a significant tumor-suppressive effect on mice HSQ-19 xenografts. These results suggest the utility of saponin treatment as an enhancer of immunotoxin treatment in cancer.

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Systemic therapy for head and neck squamous cell carcinoma: Historical perspectives and recent breakthroughs

Abstract: These findings reinforce the importance of supporting further HNSCC drug discovery as modern treatment strategies using systemic therapy have resulted in measurable improvements in oncologic outcomes. Laryngoscope, 127:2565-2569, 2017.

Cited by 28 publications

References 29 publications

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

Effectiveness Outcomes in Patients With Recurrent or Refractory Head and Neck Cancers: Retrospective Analysis of Data From a Community Oncology Database

Saponin Facilitates Anti-Robo1 Immunotoxin Cytotoxic Effects on Maxillary Sinus Squamous Cell Carcinoma

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