Table 4.
Small Molecule Tyrosine Kinase Inhibitors and CV Considerations
| Class/Target | Specific Agents | Cancer Control Mechanisms | Cardiovascular Toxicities | Proposed Mechanism of Cardiotoxicity | Cardiovascular Treatment Considerations | Ref. # |
|---|---|---|---|---|---|---|
| ALK inhibitors | Alectinib; crizotinib | Inhibition of ALK activity leading to decreased cell proliferation and angiogenesis | Bradycardia; QT prolongation | Decrease If (pacemaker current) in sinoatrial nodal cells | Avoid nodal blocking agents | (120,121) |
| BCR-ABL | Imatinib; nilotinib, dasatinib, bosutinib; ponatinib | Target BCR-ABL fusion protein, c-Kit, and platelet-derived growth factor receptors | Ischemic vascular disease; hypertension; hyperlipidemia; hyperglycemia; QT prolongation; pulmonary hypertension; pleural effusion; pericardial effusion | Accelerated atherosclerosis; endothelial dysfunction; thrombotic microangiopathy | Statins; antihyperglycemics | (80,110,111) |
| BTK inhibitor | Acalabrutinib; ibrutinib | Inhibition of the BTK pathway | Atrial fibrillation; ventricular arrhythmias; hypertension | PI3K–Akt pathway, atrial fibrosis, dysregulated calcium handling | Avoid drugs that interact with the CYP 3A4 system (i.e., dihydropyridine calcium-channel blockers) and p-glycoprotein (i.e., dabigatran) | (112,113,115,116) |
| BRAF inhibitor | Dabrafenib; vemurafenib | Selective inhibition of B-raf which blocks cellular proliferation | QT Prolongation | N/A | N/A | (122) |
| MEK inhibitor | Binimetinib; combimetinib; trametinib | Allosteric inhibition of MEK affecting the MAPK pathway | Hypertension; heart failure/left ventricular dysfunction; QT prolongation | Inhibition of ERK1/2 activation in the heart | N/A | (123,124) |
| VEGF inhibitor | Axitinib; cabozantanib; lenvatinib; pazopanib; regorafenib; sorafenib; sunitinib; vandetanib |
Inhibits vascular endothelial growth factor receptors | Hypertension; left ventricular dysfunction; QT prolongation | Decreased nitric oxide bioavailability; microvascular rarefaction; increased endothelin-1 | ACE inhibitors/angiotensin receptor blockers; dihydropyridine calcium-channel blockers for hypertension | (125) |
ACE = angiotensin-converting enzyme; ALK = anaplastic lymphoma kinase; MAPK = mitogen-activated protein kinase; VEGF = vascular endothelial growth factor.