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

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.

SUBMITTER: Bronte E

PROVIDER: S-EPMC4742127 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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

Bronte Enrico E Bronte Giuseppe G Novo Giuseppina G Bronte Fabrizio F Bavetta Maria Grazia MG Lo Re Giuseppe G Lo Re Giuseppe G Brancatelli Giuseppe G Bazan Viviana V Natoli Clara C Novo Salvatore S Russo Antonio A

Oncotarget 20151101 34

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 mol ...[more]

PMID: 26431495

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Project description:Rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized treatment for patients with BRAF-mutated melanoma. Although left ventricular systolic dysfunction associated with these therapies has been reported in clinical trials, the real-world incidence is poorly defined, as are risk factors for its development. This study sought to characterize the incidence, time course, and risk factors for cancer therapy-related cardiac dysfunction (CTRCD) in patients with melanoma receiving BRAF and MEK inhibitors. Patients with melanoma treated with BRAF and MEK inhibitors at a cancer hospital network between June 1, 2017, and June 30, 2020, were included retrospectively. CTRCD was defined as mild, moderate, or severe according to International Cardio-Oncology Society (ICOS) definitions. Baseline cardiotoxicity risk stratification was performed using the Heart Failure Association/ICOS tool. Of the 63 patients included, 27% developed CTRCD (17% mild and 10% moderate). No patients developed severe CTRCD or symptomatic heart failure. CTRCD occurred most frequently in patients considered to be at "low" and "medium" baseline risk of cardiotoxicity (82%). The baseline left ventricular ejection fraction and global longitudinal strain were not different in patients who developed moderate CTRCD vs those who did not. Left ventricular internal diameters in diastole and systole were larger in patients who developed moderate CTRCD compared with those who did not (left ventricular internal diameter in diastole: 4.9 ± 0.6 cm vs 4.3 ± 0.6 cm; P = 0.023; left ventricular internal diameter in systole: 3.3 ± 0.4 cm vs 2.8 ± 0.5 cm; P = 0.039). BRAF and MEK inhibitor-associated CTRCD is common. The utility of the Heart Failure Association/ICOS risk stratification tool appears limited in this group, and better risk prediction tools are needed. The long-term consequences of CTRCD, particularly mild CTRCD, warrant evaluation in larger prospective studies.

Dataset Information

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

Publications

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

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