The prince and the pauper. A tale of anticancer targeted agents

Table 1 Summary of noncancer drugs, their primary indication, noncancer and cancer targets

AGENT	PRIMARY INDICATION	ON-TARGET Primary effects	ON-TARGET Antitumor effects	OFF-TARGET Antitumor effects
CCA
Verapamil Diltiazem	Anti-arrhytmic	L-type Ca²⁺ channels	L-type Ca ²⁺ channels	Voltage-gated K+ channels MDR proteins
Inotropics
Digitalis	Heart failure	Na(+)/K(+)-ATPase	Na(+)/K(+)-ATPase	Death receptors Glycolysis
RAS
Losartan	Hypertension	ACE, AT₁R	AT ₁ R
Captopril	Heart failure
Antianginal
Nitroglycerin	CHD	GMP	cGMP
Alpha ₁ -adrenoceptor antagonists
Terazosin	Hypertension	A₁R	A ₁ R	EGFR
Alfuzosin	BPH
Prazosin
Vasodilator
Hydralazine	Hypertension	Unknown		DNA methylation
Antiarrhytmic
Procainamide	Arrhytmias	Na+ channels		DNMT1
Local anesthetic
Procaine	Local anesthesia	Na+ channels		DNA methylation
Antiepileptic
Valproic acid	Epilepsia	GABA ergic	Blocking NMDA Na+ channels	Class I-II HDACs PPARγ
Antidiabetics
Glitazones	Diabetes mellitus	PPARγ	PPARγ
Metformin	Diabetes mellitus	AMPK	AMPK
Antiobesity
Orlistat	Obesity	Fatty-Acid Synthase	Fatty-Acid Synthase
Cholesterol lowering agents
Statins	Cholesterolemia	HMGC	HMGC
Antimalarial
Chloroquine	Malaria	Lysosomas	Lysosomas	Autophagia
Abortive
Mifepristone	Abortion	Progesterone receptor	Progesterone receptor	MDR/MPR

Italic fonts indicate that the targets are shared by the pathological conditions (on-target effects).
Underlined fonts indicate that the antitumor effect is explained by different targets (off-target effects).
This table indicates that some "benign" conditions share molecular alterations with malignant diseases (one target-several indications).
CCA: calcium channel antagonists; RAS: renine-angiotensin-system; CHD: coronary heart disease; BPH: benign prostatic hyperplasia.

ISSN: 1476-4598