Drug repurposing for the treatment of glioblastoma multiforme

Abstract

BackgroundGlioblastoma Multiforme is the deadliest type of brain tumor and is characterized by very poor prognosis with a limited overall survival. Current optimal therapeutic approach has essentially remained unchanged for more than a decade, consisting in maximal surgical resection followed by radiotherapy plus temozolomide.Main bodySuch a dismal patient outcome represents a compelling need for innovative and effective therapeutic approaches. Given the development of new drugs is a process presently characterized by an immense increase in costs and development time, drug repositioning, finding new uses for existing approved drugs or drug repurposing, re-use of old drugs when novel molecular findings make them attractive again, are gaining significance in clinical pharmacology, since it allows faster and less expensive delivery of potentially useful drugs from the bench to the bedside. This is quite evident in glioblastoma, where a number of old drugs is now considered for clinical use, often in association with the first-line therapeutic intervention. Interestingly, most of these medications are, or have been, widely employed for decades in non-neoplastic pathologies without relevant side effects. Now, the refinement of their molecular mechanism(s) of action through up-to-date technologies is paving the way for their use in the therapeutic approach of glioblastoma as well as other cancer types.Short conclusionThe spiraling costs of new antineoplastic drugs and the long time required for them to reach the market demands a profoundly different approach to keep lifesaving therapies affordable for cancer patients. In this context, repurposing can represent a relatively inexpensive, safe and fast approach to glioblastoma treatment. To this end, pros and cons must be accurately considered.

A Simple Three-dimensional Hydrogel Platform Enables Ex Vivo Cell Culture of Patient and PDX Tumors for Assaying Their Response to Clinically Relevant Therapies

“…It is interesting to note that IC 50 values could be determined for all. While the data are early, the utility of repurposed drugs suggests a shifting trend with clinicians looking to find off-indication treatments for individual patients, especially after first-line treatment failure (24).…”

“…Finally, chloroquine is a medication used to treat for malaria and is currently undergoing phase III trials for GBM treatment (23). The use of these therapies demonstrates the desire and willingness by the clinical community to repurpose existing drugs (24). Neurospheres in VersaGel were dosed appropriately with each drug and a 3D-IC 50 value based on sphere growth was determined similar to previous experiments.…”

Drug repurposing against COVID-19: focus on anticancer agents

“…Rapamycin (sirolimus) has a long history of repositioning. It was first used as an antifungal, followed by an immunosuppressive agent in organ-transplanted patients and, more recently, also as an anticancer agent [2,10]. Its cellular target has been named mTOR (mammalian Target Of Rapamycin) after the name of the compound itself, showing specific activity toward the mTORC1 complex [11].…”

Drug repositioning in cancer: The current situation in Japan

“…Most pharmaceutical companies have already adopted in silico models for drug discovery from diverse chemical spaces . Using artificial intelligence algorithms and other bioinformatics tools, researchers have attempted to systematically identify interaction networks between drugs and protein targets . Clearly, in silico DR is a powerful technology with significant advantages, including speed and reduced costs .…”

“…Indeed, for such drugs, many resources have already been spent to develop these drugs, and their use in similar or novel indications could lead to cost savings and avoidance of risks related to drug development. Furthermore, prior extensive investigations of the pharmacokinetic and pharmacodynamic characteristics of drugs can allow researchers to avoid studies assessing drug dosage, safety and toxicity . In a previous report, Pantziarka et al summarized the advantages of DR as follows: availability of pharmacokinetic, pharmacodynamics and posology data; knowledge of safety, toxicity and adverse events; clinical experience derived from the original indications; widespread availability worldwide; understanding of the mechanisms of action and molecular targets of the drug; and low cost.…”