Abstract
Abstract Inflammatory Breast Cancer (IBC) is an aggressive cancer with a unique ability of forming tumor spheroids, which invade the dermal lymphatics causing the inflammatory phenotype. IBC cell lines and human tissues, overexpress Epidermal Growth Factor Receptor (EGFR), which has been associated with increasing IBC tumor growth rate, invasion and metastasis. Among the current therapeutic strategies for EGFR inhibition are the small molecule Tyrosine Kinase Inhibitors (TKIs). The high incidence of resistance to such therapies has greatly diminished their overall effectiveness, thus it seems feasible to identify agents that may be combined with these TKIs to provide a sustained response for IBC patients. For this reason, the purpose of this study is to investigate Reishi's therapeutic potential in IBC, focusing on the regulation of the EGFR signaling cascade and its contribution to the IBC cellular response when treated with the EGFR TKI, erlotinib. Our hypothesis is that Reishi sensitizes IBC cells to erlotinib therapy. EGFR-overexpressing SUM-149 IBC cells were treated with several concentrations of erlotinib, 0.025mg/mL Reishi, or both treatments simultaneously for 72h. Our results showed a synergistic effect when erlotinib and Reishi are used simultaneously after 72 hours of treatment. In order to study the molecular mechanism for the improved effects of the combination treatment we successfully developed an IBC erlotinib resistant cell line from the parental SUM-149 cells. Our data revealed that Reishi increases erlotinib sensitivity by inactivating AKT and extracellular signal-regulated kinase (ERK) signaling pathways. Taken together, our results provide evidence that Reishi chemosensitizes IBC cells to erlotinib therapy, highlighting its anti-IBC-therapeutic potential. This project was sponsored by NIH/NCI #1F31 CA174307 to ISA, Title V PPOHA US Department of Education #P031M105050 to UCC, NIH/RCMI #G12 MD007583 to UCC, NIH/INBRE #5P20 GM103475 to UPR/UCC and a research donation from the Commonwealth of Puerto Rico to UCC's University Center of Integral and Complementary Medicine (CUMIC)/MMM. Citation Format: Ivette Suárez-Arroyo, Michael Moraskie, Luis A. Cubano, Michelle M. Martínez-Montemayor. Ganoderma lucidum (Reishi) chemosensitizes EGFR-overexpressing inflammatory breast cancer cells to erlotinib. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3212. doi:10.1158/1538-7445.AM2014-3212
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