Evaluation of melanin-targeted radiotherapy in combination with radiosensitizing drugs for the treatment of melanoma

Hutchison, S., Rae, C. , Tesson, M., Babich, J., Boyd, M. and Mairs, R. (2014) Evaluation of melanin-targeted radiotherapy in combination with radiosensitizing drugs for the treatment of melanoma. Cancer and Oncology Research, 2(4), pp. 58-67. (doi: 10.13189/cor.2014.020403)

Abstract

The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. An [131I]-labeled benzamide - [131I]MIP-1145 - selectively targets melanin, reduces melanoma tumor burden and increases survival in preclinical models. Our purpose was to determine the potential of radiosensitizers to enhance the anti-tumor efficacy of [131I]MIP-1145. Melanotic (A2058) and amelanotic (A375 and SK-N-BE(2c)) cells were treated with [131I]MIP-1145 as a single agent or in combination with drugs with radiosenitizing potential. Cellular uptake of [131I]MIP-1145 and toxicity were assessed in monolayer culture. The interaction between radiosensitizers and [131I]MIP-1145 was evaluated by combination index analysis in monolayer cultures and by delayed growth of multicellular tumor spheroids. [131I]MIP-1145 was taken up by and was toxic to melanotic cells but not amelanotic cells. Combination treatments comprising [131I]MIP-1145 with the topoisomerase inhibitor topotecan or the PARP-1 inhibitor AG014699 resulted in synergistic clonogenic cell kill and enhanced delay of the growth of spheroids derived from melanotic melanoma cells. The proteasome inhibitor bortezomib had no synergistic cytotoxic effect with [131I]MIP-1145 and failed to enhance the delay of spheroid growth. Following combination treatment of amelanotic cells, neither synergistic clonogenic cell kill nor enhanced growth delay of spheroids was observed.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Rae, Dr Colin and Tesson, Dr Mathias and Hutchison, Dr Sharon and Mairs, Professor Robert and Boyd, Dr Marie
• Authors: Hutchison, S., Rae, C., Tesson, M., Babich, J., Boyd, M., and Mairs, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancer and Oncology Research
• Publisher: Horizon Research Publishing
• ISSN: 2331-6128
• ISSN (Online): 2331-6136
• Copyright Holders: Copyright © 2014 Horizon Research Publishing
• First Published: First published in Cancer and Oncology Research 2(4):58-67
• Publisher Policy: Reproduced under a Creative Commons License