New sources of drugs for hematologic malignancies

Abstract

Advancing novel therapeutic agents for the treatment of malignancy into the marketplace is an increasingly costly and lengthy process. As such, new strategies for drug discovery are needed. Drug repurposing represents an opportunity to rapidly advance new therapeutic strategies into clinical trials at a relatively low cost. Known on-patent or off-patent drugs with unrecognized anticancer activity can be rapidly advanced into clinical testing for this new indication by leveraging their known pharmacology, pharmacokinetics, and toxicology. Using this approach, academic groups can participate in the drug discovery field and smaller biotechnology companies can "de-risk" early-stage drug discovery projects. Here, several scientific approaches used to identify drug repurposing opportunities are highlighted, with a focus on hematologic malignancies. In addition, a discussion of the regulatory issues that are unique to drug repurposing and how they impact developing old drugs for new indications is included. Finally, the mechanisms to enhance drug repurposing through increased collaborations between academia, industry, and nonprofit charitable organizations are discussed.

Figure 1

Time line for de novo drug discovery. When developing a new drug, the compound requires complete preclinical characterization, including ADME profiling, and toxicology testing. Suitable compounds require formulation and manufacturing before advancing into clinical trials.

Figure 2

Time line for drug repurposing. Drug repurposing leverages the prior toxicology and pharmacology testing of the compounds to enable rapid progression into clinical trial. At times, new formulation and manufacturing are required. Representative drug repurposing examples are shown along with their time lines.