Omics-driven drug repurposing as a source of innovative therapies in rare cancers

ABSTRACT

Introduction: Despite the relatively high prevalence of rare cancers as a collective group, the low incidence for individual rare and ultrarare cancers continues to act as an impediment to the development of new therapeutic molecules. One response to this situation is the increased use of the precision medicine paradigm for rare cancers.

Areas covered: Innovative treatment approaches can be explored based on the genotype of individual tumors, thus bypassing the issue of the high genetic heterogeneity of many rare tumor types. Identification of specific molecular targets and pathways allows the selection of candidate drugs aimed at those targets. A number of illustrative examples, in a range of rare cancers, are outlined in this paper. Data from the Repurposing Drugs in Oncology project include more than 240 candidate drugs with a broad range of identified targets and is supportive of this approach.

Expert opinion: The repurposing of non-cancer drugs extends the reach of precision medicine by widening the search space of drug targets. The repurposing of generic non-cancer medications is therefore a source of innovative therapies in rare cancers and should be considered in all precision medicine trials and initiatives.

KEYWORDS:

• Drug repurposing
• precision oncology
• rare cancers
• personalized medicine
• drug repositioning

Article highlights

• The precision oncology approach is being increasingly investigated for the treatment in the rare cancers arena, both in the form of clinical trials and as off-trial off-label treatments.

• Drug repurposing – the use of existing licensed medicines for new indications – is also increasingly being used to investigate possible new treatment options for rare cancers.

• The repurposing of generic drugs is problematic due to financial obstacles that are not completely addressed by Orphan Drug Designation.

• A number of examples of molecularly guided drug repurposing are outlined to show how the precision oncology and drug repurposing approaches align.

• Including non-cancer drugs in the armory of precision oncology, both in trials and clinical practice, increases the range of actionable targets and can therefore lead to patient benefit

• If a strong signal is seen, as in the case of angiosarcoma and propranolol, prospective clinical trials are required to prove efficacy. Ultimately, the aim is for the repurposed drug to be licensed for the new indication and to become a standard of care treatment.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.