Abstract B20: Combination of Ganoderma lucidum extract and erlotinib decreases IBC progression

Inflammatory breast cancer (IBC) is a rare, and the most lethal and aggressive type of advanced breast cancer. Despite many efforts to increase IBC treatment efficacy, prognosis of this cancer is very grim. IBC cells and tissues overexpress epidermal growth factor receptor (EGFR), and this is a poor prognostic factor in this disease. Erlotinib is a small oral EGFR tyrosine kinase inhibitor that causes reverse inhibition of the EGFR tyrosine kinase domain. However, Erlotinib resistance can reduce the efficacy of this treatment. Our published results demonstrate that the extract of medicinal mushroom, Ganoderma lucidum (GLE), selectively decreases IBC cell viability. Our hypothesis is that the combination of GLE and Erlotinib will be more effective than their treatments alone, in reducing cancer cell viability and tumor progression via the EGFR signaling pathway. The IBC cell line, SUM149, was treated with Erlotinib and GLE at different concentrations for 72hrs to examine cell viability. To determine tumor progression, severe combined immunodeficient (SCID) mice were injected with SUM149 cells and then treated with Erlotinib alone, and in combination with GLE for 13 weeks. The expression of extracellular signal-regulated kinase (ERK)-1/2 and serine/threonine-specific protein kinase (AKT) of tumor samples were studied by Western Blot analysis, as the interaction of these signaling pathways are important in drug resistance effects and tumorigenesis. Our results show that SUM149 cells treated with Erlotinib and/or GLE decrease their viability in a dose-dependent manner. Moreover, using both treatments in combination at lower dosages than those alone results in reduced viability. In vivo results show that during weeks 8 to 13 of treatment, tumor volume in Erlotinib plus GLE treated mice was significantly lower when compared to tumor volume in Erlotinib treated mice. Also, Erlotinib alone and Erlotinib plus GLE treated mice displayed significantly reduced tumor weight when compared with their respective controls. Tumor lysate analysis shows that Erlotinib plus GLE treated mice have significant lower expression of total ERK-1/2 and total AKT in their tumors when compared with Erlotinib treated mice. Our results suggest that the combination of Erlotinib with GLE may be affecting the downstream EGFR signaling pathway. We conclude that a combinatorial therapeutic approach might be the best way to increase prognosis in IBC patients. This project was sponsored by NIH/NCI #1F31CA174307 to ISA, Title V PPOHA US Department of Education #P031M105050 to UCC, NIH/RCMI #G12MD007583 to UCC/MMM, NIH/INBRE #5P20 GM103475 to UPR/UCC/MMM, NIH/SC3 #SC3GM111171 to UCC/MMM and NIH/NIGMS R25GM110513 to UCC/LAC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the supporting agencies. Citation Format: Tiffany J. Rios-Fuller, Ivette J. Suarez-Arroyo, Mercedes Lacourt-Ventura, Geronimo Maldonado, Luis A. Cubano, Michelle M. Martinez-Montemayor. Combination of Ganoderma lucidum extract and erlotinib decreases IBC progression. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr B20.