Eribulin inhibits tumor growth of two novel patient-derived xenograft models of Merkel cell carcinoma

Abstract

Background

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with a poor prognosis in advanced cases. Despite reported sensitivities to chemotherapy and immunotherapy, response rates remain limited to approximately 50 % of cases. Although developing novel therapeutic strategies against MCC has been desired, few preclinical models, including cell lines and patient-derived xenografts (PDXs), are available.

Objectives

This study aimed to establish novel preclinical research models and develop novel therapeutic strategies for MCC.

Methods

We analyzed 19 clinical MCC samples in our department. Moreover, to establish novel PDX tumors, we transplanted MCC tissues from Japanese patients into immunodeficient NOD/SCID mice.

Results

Histopathological analyses of 19 clinical MCC samples in our department revealed the tumors to either be infected with the Merkel cell polyomavirus or have lost the expression of tumor suppressors (tumor protein p53 [p53] or RB transcriptional corepressor 1 [Rb1]). To establish novel PDX tumors, we transplanted MCC tissues from Japanese patients into immunodeficient NOD/SCID mice. Two MCC-PDX tumors were successfully implanted (MCC-PDX-MK1 and -MK2), and their histopathological and genetic characteristics were consistent with those of the original tumor. As in vivo preclinical treatments, we administered cisplatin, etoposide, docetaxel, or eribulin to the NOD/SCID mice. Eribulin showed antitumor activity in both MCC-PDX models.

Conclusion

Two MCC-PDX models were established successfully, and therapeutic experiments suggest that eribulin could inhibit MCC tumor growth.