Abstract 4381: MiR-205 and Trastuzumab: Potential as adjuvant therapeutic tool and predictive biomarker

Despite the improvement in the management of HER2+ breast cancer patients with the approval of Trastuzumab in the clinical practise, and the success rate of this treatment, a still considerable percentage of patients do not respond or eventually develop a secondary resistance, leading to relapse and poor outcome. A crucial issue is represented by the urgent need of biomarkers able to predict the response to treatment, and certainly of new therapeutic tools to counteract the resistance mechanisms. It is known that resistance to anti-HER2 therapies can be due to escape mechanisms triggered by alternative receptors: here we show that HER3 silencing, either mediated by miR-205, known to directly target the receptor (Iorio MV et al., 2009) or by a siRNA specific against HER3, is able to improve the responsiveness to Trastuzumab, reducing tumor cell growth and colony formation capability. This effect seems to be mediated by impairment of the Akt-mediated pathway. Finally, evaluating miR-205 expression in a series of 51 HER2+ breast cancer patients treated with Trastuzumab in adjuvant setting, we observed that miR-205 is significantly associated with outcome: setting the median expression as cut-off, and performing a contingency analysis (Fisher's exact test), miR-205 expression was above the median in a significantly (p=0.03) higher percentage of responders versus non responders patients (61% versus 26%). In summary, here we show that miR-205 improves the responsiveness to Trastuzumab treatment at least partially though HER3 silencing, and associated to outcome of patients treated in adjuvant setting, thus representing a potential adjuvant tool and predictive biomarker. Citation Format: Elvira D'Ippolito, Claudia Piovan, Ilaria Plantamura, Marta Giussani, Patrizia Casalini, Manuela Campiglio, Elda Tagliabue, Marilena V. Iorio. MiR-205 and Trastuzumab: Potential as adjuvant therapeutic tool and predictive biomarker. [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 4381. doi:10.1158/1538-7445.AM2014-4381