Introduction
Cancer is one of the leading causes of disease burden and mortality in the world, and its presence continues to challenge health care systems worldwide. Conventional drug discovery and development are said to be costly, time-consuming, and associated with high failure rates. However, in the past years, the concept of drug repositioning has emerged as a highly potential strategy to reduce these difficulties, especially in the area of oncology. Drug repositioning, on the other hand, is the process of identifying new therapeutic uses for existing drugs that have already been approved for other conditions. This is thought to be an approach of great recent interest because it allows the reduction of time, cost, and risk in developing new cancer therapies. With safety and pharmacokinetic data available, drug repurposing will enable translational investigations from the bench and a quick move toward effective treatments for patients. In this review, I discuss drug repurposing in oncology, including key examples and mechanisms through which these drugs show their anticancer effects.
The Rationale for Drug Repurposing in Oncology
Classical drug discovery is long, with an expensive proposition running into multiple decades and billions of dollars for the development of a new drug. Cancer adds complexity and heterogeneity, with drug repurposing offering a real solution through the already large repository of drugs available for utilization, many of which have well-characterized safety profiles. The approach not only saves time and resources, but the laboratory findings can be translated into clinical settings very quickly.
In the field of oncology, a particular concern is the demand for effective therapies against the backdrop of rapid disease progression. In this area, drug repurposing is a potent method to radically shorten the period of remedial search. Repurposed molecules often treat diseases through new MOAs, which have not been targeted by standard cancer therapy till now, thus providing an assurance of an effective treatment for a cancer patient who has refractory or resistant cancer.
The mechanistic action of repurposed oncology drugs involves multiple targetings of various pathways involved in cancer progression. Few repurposed drugs exploit mechanisms concerned with their original indications, giving an anti-cancer effect. No steroidal anti-inflammatory drugs, a very common pain-relieving and anti-inflammatory agent, have been found to have anti-cancer properties by COX inhibition. However, recently, it has been shown in studies that it can target other pathways involving NSAIDs in apoptosis and immune modulation, thereby making them a potent candidate for cancer therapy.
In addition, other antiprotozoal drugs, like atovaquone, developed mainly for the treatment of parasitic infections, have promising effects in inhibiting the growth of different cancers, which may include breast cancer. Atovaquone inhibits the pathway of signaling HER2/β-catenin, which is important for the viability and multiplication of cancer cells. Through this type of dual targeting, the treatment becomes effective, and the development of resistance is unlikely.
A striking example is the use of antimalarial agents in the treatment of cancer. Pyrimethamine, an inhibitor of the dihydrofolate reductase in the parasite responsible for causing malaria, has also been identified as an anti-cancer agent for similar reasons, that is, against the same targets in the folate pathway of tumor cells. Interestingly, its recent identification as an inhibitor of EMT, which is key to cancer metastasis, has added to its credentials as a drug repositioned for cancer treatment.