Abstract
Cancer is a complex group of diseases that constitute the second largest cause of mortality worldwide. The development of new drugs for treating this disease is a long and costly process, from the discovery of the molecule through testing in phase III clinical trials, a process during which most candidate molecules fail. The use of drugs currently employed for the management of other diseases (drug repurposing) represents an alternative for developing new medical treatments. Repurposing existing drugs is, in principle, cheaper and faster than developing new drugs. Antihypertensive drugs, primarily belonging to the pharmacological categories of angiotensin-converting enzyme inhibitors, angiotensin II receptors, direct aldosterone antagonists, β-blockers and calcium channel blockers, are commonly prescribed and have well-known safety profiles. Additionally, some of these drugs have exhibited pharmacological properties useful for the treatment of cancer, rendering them candidates for drug repurposing. In this review, we examine the preclinical and clinical evidence for utilizing antihypertensive agents in the treatment of cancer.
Highlights
Cancer is the second leading cause of mortality in individuals younger than 70 years, just after cardiovascular diseases [1]
Antihypertensive drugs can be classified into four main groups according to their mechanism of action: those that act in the renin angiotensin aldosterone system (RAAS), either by inhibiting angiotensin converting enzyme (ACE), blocking the angiotensin type 1 receptor (AT1R), directly inhibiting renin action, or by antagonizing aldosterone binding to its receptor; those that act blocking the calcium channels, which can block either dihydropyridine or non-dihydropyridine calcium channels; beta blockers that block the b-adrenergic receptors; and diuretics, which decrease the volume in the circulatory system [21]
The results showed that captopril reduced the number of malignant preneoplastic lesions and the amount of DNA damage in the colon, showing that there is an important relationship between ACE activityand cancer, considering that captopril is a RAAS inhibitor and may nullify some of the oncogenic effects of azomethane by attenuating chronic inflammation and reducing oxidative stress [67]
Summary
The development of new drugs for treating this disease is a long and costly process, from the discovery of the molecule through testing in phase III clinical trials, a process during which most candidate molecules fail. The use of drugs currently employed for the management of other diseases (drug repurposing) represents an alternative for developing new medical treatments. Antihypertensive drugs, primarily belonging to the pharmacological categories of angiotensin-converting enzyme inhibitors, angiotensin II receptors, direct aldosterone antagonists, b-blockers and calcium channel blockers, are commonly prescribed and have well-known safety profiles. Some of these drugs have exhibited pharmacological properties useful for the treatment of cancer, rendering them candidates for drug repurposing.
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