Repurposing of Anticancer Stem Cell Drugs in Brain Tumors

Abstract

Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration–approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level.

Repurposed Effect of 177Lu-DOTATATE in the Treatment of Mantle Cell Lymphoma

“…Driven by the advancements in discovering the genetic and epigenetic alterations of tumor cells, this promising approach is expected to provide novel pharmacological agents that overpass the resistance to conventional therapy that is expressed in multiple cancers [ 15 , 16 ]. The repurposed effect of many medications has been studied in colorectal cancer [ 17 ], pancreatic cancer [ 18 ], and brain tumors [ 19 , 20 ]. Moreover, non-Hodgkin lymphoma has also been targeted in drug repurposing studies.…”

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing

“…Lately, researchers and clinicians are exploring drug repurposing to overcome the shortage of medication for novel cancer treatments [ 102 , 103 , 104 ]. As such, repurposing drugs with tolerable side effects and known pharmacokinetics and pharmacodynamics profiles offers an alternative to standard anti-cancer chemotherapeutics [ 51 ].…”

“…These advantages mainly revolve around time and cost, where a study by Kaitin et al showed that it takes approximately 8.3 years for an anti-cancer medication to get approved, compared with 3 to 4 years for a repurposed drug [ 105 ]. Additionally, among the various advantages of drug repurposing is being cost-effective, where a repurposed drug is estimated to cost USD 300 million to reach market, compared with USD 2–3 billion for studying a new chemical entity [ 104 , 106 ].…”

Effects of Lovastatin on Brain Cancer Cells

“…Glioblastomas (GBM) contain CSCs located in the tumor bulk 38 . CSCs in GBM contribute to tumor initiation, recurrence, and resistance to chemotherapy and radiotherapy.…”