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Supplementary Figure S7. Total volume data for EGCG plus cetuximab in sensitive and resistant TNBC ortoxenograft. from Preclinical Evaluation of Fatty Acid Synthase and EGFR Inhibition in Triple-Negative Breast Cancer

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posted on 2023-03-31, 19:24 authored by Ariadna Giró-Perafita, Sònia Palomeras, David H. Lum, Adriana Blancafort, Gemma Viñas, Glòria Oliveras, Ferran Pérez-Bueno, Ariadna Sarrats, Alana L. Welm, Teresa Puig

(A) Mice bearing 231 and (B) 231DXR xenografts were treated with saline (Control), EGCG (30mg/Kg, 3 days a week), cetuximab (0.5mg/mice 1 day a week) or the combination (EGCG plus cetuximab) for 12 days. (C) Mice bearing HCC and (D) HCCDXR xenografts were treated with saline (Control), EGCG (30mg/Kg, 3 days a week), cetuximab (100uL/mice 1 day a week) or the combination (EGCG plus cetuximab) for 10 days. Total volume is shown as (Final Volume - Initial Volume). Dots are mean of each experimental group and bars, SEM. *(p < 0.05), **(p < 0.01) and ***(p < 0.001) indicate levels of statistically significance.

Funding

Instituto de Salud Carlos III

Fundación Ramón Areces

Catalonian Government

U.S. Department of Defense

XBTC

Metavivor Research and Suport Inc

University of Girona

History

ARTICLE ABSTRACT

Purpose: Triple-negative breast cancer (TNBC) lacks an approved targeted therapy. Despite initial good response to chemotherapy, 30% of the patients relapse within 5 years after treatment. EGFR overexpression is a common marker in TNBC, and its expression has been correlated with poor outcome. Inhibition of fatty acid synthase (FASN) activity leads to apoptosis of human carcinoma cells overexpressing FASN. We tested the hypothesis that blocking FASN in combination with anti-EGFR signaling agents would be an effective antitumor strategy in sensitive and chemoresistant TNBC.Experimental Design: Several TNBC cell lines and 29 primary tumors were included to determine whether FASN is a potential target in TNBC. Doxorubicin-resistant TNBC cell lines (231DXR and HCCDXR) have been developed and characterized in our laboratory. Cellular and molecular interactions of anti-FASN compounds (EGCG and C75) with cetuximab were analyzed. In vivo tumor growth inhibition was evaluated after cetuximab, EGCG, or the combination in TNBC orthoxenograft models.Results: TNBC cell lines showed overexpression of FASN enzyme and its inhibition correlated to FASN levels. FASN staining was observed in all of the 29 TNBC tumor samples. In vitro, EGCG and C75 plus cetuximab showed strong synergism in sensitive and chemoresistant cells. In vivo, the combination of EGCG with cetuximab displayed strong antitumor activity against the sensitive and chemoresistant TNBC orthoxenografts, without signs of toxicity.Conclusions: Our results show that the simultaneous blockade of FASN and EGFR is effective in preclinical models of sensitive and chemoresistant TNBC. Clin Cancer Res; 22(18); 4687–97. ©2016 AACR.

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