Oncotarget

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What links BRAF to the heart function? new insights from the cardiotoxicity of BRAF inhibitors in cancer treatment

Enrico Bronte, Giuseppe Bronte, Giuseppina Novo, Fabrizio Bronte, Maria Grazia Bavetta, Giuseppe Lo Re, Giuseppe Brancatelli, Viviana Bazan, Clara Natoli, Salvatore Novo and Antonio Russo _

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Oncotarget. 2015; 6:35589-35601. https://doi.org/10.18632/oncotarget.5853

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Abstract

Enrico Bronte1,*, Giuseppe Bronte1,*, Giuseppina Novo2,*, Fabrizio Bronte3, Maria Grazia Bavetta3, Giuseppe Lo Re4, Giuseppe Brancatelli4, Viviana Bazan1, Clara Natoli5, Salvatore Novo2 and Antonio Russo1

1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy

2 Department of Internal Medicine and Cardiovascular Disease, University of Palermo, Palermo, Italy

3 DiBiMIS, Section of Gastroenterology, University of Palermo, Palermo, Italy

4 Department of Radiology, University of Palermo, Palermo, Italy

5 Department of Medical, Oral and Biotechnological Sciences, University “G. D’Annunzio”, Chieti, Italy

* These authors contributed equally to this work

Correspondence to:

Antonio Russo, email:

Keywords: B-RAF, B-RAF inhibitors, cardio-oncology, cardiotoxicity, dabrafenib

Received: August 04, 2015 Accepted: August 22, 2015 Published: September 28, 2015

Abstract

The RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolongation. Though this cardiovascular side effect is not common using these drugs, it must be noticed early and recognize its signals. Indeed, Oncologists and Cardiologists should work in cooperation to prevent lethal events, such as fatal arrhythmias or sudden cardiac death. These events could originate from an uncontrolled QT prolongation.


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