Abstract
Platinum-based therapy is most often used to treat advanced cases of head and neck cancers, but only a small fraction of the patient population responds to cisplatin, with a median survival time of less than a year. Although gene signatures and molecular etiology of head and neck cancers have been previously described, none of them are predictive indicators of cisplatin treatment response in particular. Therefore, currently, there is a lack of clinically employable predictive indicators of the disease beyond HPV status to specifically predict patients' response to platinum-based therapy. It beckons a substantial effort to look for predictive indicators of cisplatin treatment response. In this regard, CD24 expression level appears to be a significant molecular phenotype of cisplatin-resistant residual cells in laryngeal carcinoma lines. CD24 expression level directly affects cisplatin sensitivity and affects the expression of critical apoptotic, stem and drug resistance genes. A relatively small retrospective patient tumor analysis suggests that CD24 high tumors go on to show an unfavorable response to cisplatin treatment. Overall, based on the strength of further analysis, CD24 presents a strong rationale to be utilized as a predictive indicator to stratify head and neck cancer patients for platinum-based therapy. It also provides a rationale for using CD24 as a therapeutic adjuvant target along with standard cisplatin therapy.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is a cluster of biologically similar cancers that originate from the mucosal squamous epithelial lining of the upper aerodigestive tract
To investigate whether CD44 percentage correlates with cisplatin resistance in laryngeal carcinoma; we chose three laryngeal carcinoma cell lines namely, UM-SCC-10B, UM-SCC-15s and UM-SCC-74B (Fig 1A)
Once the cisplatin IC-50 values of the three HNSCC lines were determined, analysis of the three cell lines with CD44 monoclonal antibody in a flow cytometer was performed. It demonstrated that CD44 percentage is overwhelmingly high (~97%) in all these three HNSCC lines irrespective of their varying cisplatin sensitivities (Fig 1C and 1D)
Summary
Head and neck squamous cell carcinoma (HNSCC) is a cluster of biologically similar cancers that originate from the mucosal squamous epithelial lining of the upper aerodigestive tract. HNSCC have high cure rates, up to 50% of patients present with advanced disease [1]. Patients presenting with advanced disease of HNSCC are associated with a high mortality rate. Close to 50% of advanced HNSCC tumors relapse within the first 24 months of treatment [2] [3]. Cisplatin-based chemotherapy is the most commonly used treatment for advanced cases, but only about 10–35% responds to cisplatin, with a median survival time of 6–12 months [4]. There is a lack of clinically employable predictive indicators of the disease beyond HPV status to predict patients' response to platinum-based therapy [5]. To look for potential predictors of cisplatin treatment response to classify patients who may or may not benefit from platinum-based therapy is paramount
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