TY - JOUR
T1 - Cardiotoxicity mechanisms of the combination of BRAF-inhibitors and MEK-inhibitors
AU - Bronte, Giuseppe
AU - Passiglia, Francesco
AU - Russo, Antonio
AU - Novo, Giuseppina
AU - Bronte, Fabrizio
AU - Rinaldi, Gaetana
AU - Bronte, Fabrizio
AU - Russo, Antonio
AU - Passiglia, Francesco
AU - Bronte, Enrico
AU - Bronte, Giuseppe
AU - Bronte, Enrico
PY - 2018
Y1 - 2018
N2 - Many new drugs have appeared in last years in the oncological treatment scenario. Each drug carries an important set of adverse events, not less, cardiovascular adverse events. This aspect is even more important considering the increasing use of combination therapies with two drugs, or three drugs as in some ongoing clinical trials. Besides it represents a growing problem for Cardiologists, that face it in every day clinical practice and that will face it probably more and more in the coming years. This work reviews the mechanism of action of BRAF-inhibitors and MEK-inhibitors used together, the pathophysiological mechanisms that lead to cardiovascular toxicity. Particularly, it focuses on hypertension and ejection fraction reduction development. Then, it follows the examination of published data for each combination therapy. A Literature research was carried out using Pubmed selecting review articles, original studies and clinical trials, but mainly focusing on phase 3 studies. This work aims to summarize the knowledge about BRAF-inhibitor and MEK-inhibitor treatment and its cardiovascular toxicity to make it usable and give the basic tools to Cardiologists and Oncologists for a better management of cancer patient undergoing this treatment. Besides a deeper knowledge of the cardiovascular adverse events linked to this treatment and the magnitude of their expression and frequency can lead to a targeted cardiological treatment.
AB - Many new drugs have appeared in last years in the oncological treatment scenario. Each drug carries an important set of adverse events, not less, cardiovascular adverse events. This aspect is even more important considering the increasing use of combination therapies with two drugs, or three drugs as in some ongoing clinical trials. Besides it represents a growing problem for Cardiologists, that face it in every day clinical practice and that will face it probably more and more in the coming years. This work reviews the mechanism of action of BRAF-inhibitors and MEK-inhibitors used together, the pathophysiological mechanisms that lead to cardiovascular toxicity. Particularly, it focuses on hypertension and ejection fraction reduction development. Then, it follows the examination of published data for each combination therapy. A Literature research was carried out using Pubmed selecting review articles, original studies and clinical trials, but mainly focusing on phase 3 studies. This work aims to summarize the knowledge about BRAF-inhibitor and MEK-inhibitor treatment and its cardiovascular toxicity to make it usable and give the basic tools to Cardiologists and Oncologists for a better management of cancer patient undergoing this treatment. Besides a deeper knowledge of the cardiovascular adverse events linked to this treatment and the magnitude of their expression and frequency can lead to a targeted cardiological treatment.
KW - BRAF inhibitor
KW - Cardio-oncology
KW - Cardiovascular toxicity
KW - Decreased ejection fraction
KW - Hypertension
KW - MEK inhibitor
KW - Pharmacology
KW - Pharmacology (medical)
KW - BRAF inhibitor
KW - Cardio-oncology
KW - Cardiovascular toxicity
KW - Decreased ejection fraction
KW - Hypertension
KW - MEK inhibitor
KW - Pharmacology
KW - Pharmacology (medical)
UR - http://hdl.handle.net/10447/298745
UR - http://www.elsevier.com/locate/pharmthera
M3 - Article
JO - PHARMACOLOGY & THERAPEUTICS
JF - PHARMACOLOGY & THERAPEUTICS
SN - 0163-7258
ER -