Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists’ arsenal

Abstract

Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of distinct commercially available pharmacological agents that are not currently used in the field of oncology, ie, nonsteroidal anti-inflammatory drugs, antihypertensive agents, and anti-human immunodeficiency virus agents inhibiting viral protease, are reviewed. The aim is to provide integrated information regarding not only the molecular basis of the antitumor function of these agents but also the applicability of the reevaluation of their therapeutic range in the clinical setting.

Marketed drugs used for the management of hypercholesterolemia as anticancer armament

“… 1 , 2 Importantly, a growing body of evidence suggests that several pharmacologic agents could be “repositioned” or “repurposed” in the field of oncology, owing to their interference with signaling pathways which are crucial for tumorigenesis. This notion is experimentally (at the preclinical level, clinical level or even at both levels) corroborated for marketed agents currently used for the management of different pathologic entities ranging from pain, 3 gastrointestinal disorders, 4 depression, 5 hypercholesterolemia 6 and diabetes mellitus type II 7 , 8 to human immunodeficiency virus 9 , 10 and parasitic infection. 11 , 12 …”

“… 186 Aspirin, similar to statins, is a widely prescribed NSAID with well-established antitumor properties. 9 , 187 Caffeine is commonly combined with aspirin in commercially available formulations and is also well known to exhibit antitumor function. 188 – 190 Serum proteomics data ( Figure S1 ) indicate that at the clinical level, administration of aspirin combined with caffeine compared to aspirin alone may affect (either positively or negatively) the levels of proteins in human serum that have been linked to cancer biology, cancer prognosis/diagnosis and prediction of the efficacy of anticancer medication.…”

“… 194 These hints would be very interesting to be experimentally validated in the future. Paradoxically enough, although several experimental data have been provided so far regarding the multilevel pharmacologic activity of aspirin or caffeine alone, 9 , 195 – 198 only less amount of data has been published regarding the effects of aspirin combined with caffeine. 199 , 200 Most importantly, research so far has focused on the analgesic properties of this combinational scheme.…”

Unexploited Antineoplastic Effects of Commercially Available Anti-Diabetic Drugs

“…This is widely known as drug “repurposing” or “repositioning” in oncology. Paying credence to this emerging concept, diverse commercially available non-antineoplastic agents such as anti-hypercholesterolemic agents [ 12 ], nonsteroidal anti-inflammatory drugs (NSAIDs), agents currently used for the management of hypertension or even agents received by patients suffering from acute immunodeficiency syndrome (AIDS) exhibit profound anti-cancer activity [ 13 , 14 , 15 ].…”

In vivo and in vitro interaction studies of ibuprofen with enalapril

“…Therefore, the prostaglandin system could be involved in the mechanism of action of ACE inhibitors. A human reduction of the antihypertensive activity of captopril was observed when NSAIDs, especially ibuprofen were administered [4].…”