Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display

1577 - Ranolazine partially blunts ado trastuzumab emtansine related cardiotoxicity


10 Oct 2016


Poster display


Nicola Maurea


Annals of Oncology (2016) 27 (6): 1-14. 10.1093/annonc/mdw362


N. Maurea1, C. Coppola1, G. Piscopo1, G. Riccio1, A. Rienzo1, C. Maurea1, A. Barbieri2, C. De Lorenzo3, R.V. Iaffaioli4

Author affiliations

  • 1 Cardiology, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, 80131 - Napoli/IT
  • 2 Animal Facility, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, 80131 - Napoli/IT
  • 3 Department Of Molecular Medicine And Medical Biotechnology, University ‘Federico II’, Napoli/IT
  • 4 Abdominal Oncology, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, 80131 - Napoli/IT


Abstract 1577


Ado trastuzumab emtansine (TDM1) is a novel antibody–drug conjugate consisting of trastuzumab (TRAS) covalently linked to the highly potent microtubule inhibitory agent DM1 via a stable thioether linker. TDM1 is used in metastatic ErbB2 positive breast cancer patients. Although, the potential cardiotoxic effects of TDM1 have not yet been fully elucidated, they can include all the mechanisms of TRAS-related cardiotoxicity, such as changes in Ca2+ regulation. Here, we aim to elucidate whether Ranolazine (RAN), administered after TDM1 treatment, blunts or not cardiotoxicity in vivo and in vitro.


In vitro, human fetal cardiomyocytes (HFC) were treated with TDM1 for 3 days and then treated in the absence or presence of RAN for 3 days. Cell viability was assessed by cell counting and MTT assay. To evaluate cardiac function in vivo, C57/BL6 mice, 2-4 months old, were daily treated with TDM1 (44.4 mg/kg/day). At day 0 and after 7 days, fractional shortening (FS) and ejection fraction (EF) were measured, by M/B mode echocardiography, and radial and longitudinal strain (RS and LS) were evaluated using 2D speckle-stracking. These measurements were repeated after 5 days of RAN treatment (305 mg/Kg/day), started at the end of TDM1 treatment.


RAN reduces TDM1 toxicity in HFC, as evidenced by the higher percentage of viable cells treated with TDM1+ RAN with respect to the cells treated with TDM1 alone (p 


Here we show that in vivo RAN post-treatment reduces cardiotoxic effects due to TDM1, as demonstrated by the recovery of FS, EF and LS values. As expected, RAN increases cell viability of HFC treated with TDM1.

Clinical trial identification

Legal entity responsible for the study



Fondi di Ricerca Corrente destinati all' Istituto Nazionale Tumori Pascale - Napoli


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings