Prediction of response to radiotherapy in the treatment of esophageal cancer using stem cell markers

Abstract

Background and purpose: In this study, we investigated whether cancer stem cell marker expressing cells can be identified that predict for the response of esophageal cancer (EC) to CRT. Materials and methods: EC cell-lines OE-33 and OE-21 were used to assess in vitro, stem cell activity, proliferative capacity and radiation response. Xenograft tumors were generated using NOD/SCID mice to assess in vivo proliferative capacity and tumor hypoxia. Archival and fresh EC biopsy tissue was used to confirm our in vitro and in vivo results. Results: We showed that the CD44+/CD24À subpopulation of EC cells exerts a higher proliferation rate and sphere forming potential and is more radioresistant in vitro, when compared to unselected or CD44+/CD24+ cells. Moreover, CD44+/CD24À cells formed xenograft tumors faster and were often located in hypoxic tumor areas. In a study of archival pre-neoadjuvant CRT biopsy material from EC adenocarcinoma patients (N = 27), this population could only be identified in 50% (9/18) of reduced-responders to neoadjuvant CRT, but never (0/9) in the complete responders (P = 0.009). Conclusion: These results warrant further investigation into the possible clinical benefit of CD44+/CD24À as a predictive marker in EC patients for the response to chemoradiation.

Tumor recurrence and in-field control after multimodality treatment of locally advanced esophageal cancer

“…Recently, Smit et al showed that CD44+/CD24À EC tumor cells contain more in vitro radioresistant properties than CD44+/CD24+ cells. Furthermore, this was confirmed by analysis of archival pre-CRT biopsy material of 27 patients with AC, as none of the 9 complete responders contained CD44+/CD24À tumor cells [29]. The radioresistant properties of tumor cells might be intrinsic to certain tumor subtypes, but might also be induced during radiotherapy by a mechanism called the tumor-bed-effect [30].…”

Peritoneal Tumor Carcinomatosis: Pharmacological Targeting with Hyaluronan-Based Bioconjugates Overcomes Therapeutic Indications of Current Drugs

“…The following human tumor cell lines were used: HCT-15 [34], HT-29 [35] and LoVo [36], colorectal adenocarcinoma; OE-33 [37], esophageal adenocarcinoma; KYSE-30 [38] and OE-21 [37], esophageal squamous carcinoma; MKN-45 [39], gastric adenocarcinoma. A CD44 high subpopulation of HCT-15 was isolated by immunomagnetic sorting, as previously reported [40].…”

Nomogram for predicting pathologically complete response after neoadjuvant chemoradiotherapy for oesophageal cancer

“…In this context recent studies have shown promising markers such as stem cell markers in oesophageal cancer [44] and microRNAs as predictive biomarkers for response [45]. These findings have not yet been validated and their clinical relevance needs to be further elucidated.…”