Opinion
Potential Reuse of Oncology Drugs in the Treatment of Rare Diseases

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Trends

Evidence suggests that germline mutations associated with rare diseases may predispose patients to develop somatic mutations that trigger tumor development.

In some cases, cancers and rare diseases may perturb the same biological pathways, suggesting the possibility of shared therapeutic targets.

Anticancer drugs may therefore have potential to be repurposed to treat some rare genetic diseases.

Cancer research has made remarkable progress with the help of advancing genomics techniques, resulting in more precise clinical application and many new anticancer drugs on the market. By contrast, very few treatment options are available for rare diseases that are often progressive, severe, and life-threatening. In this opinion we elaborate on the possible association between cancers and rare diseases across three different levels including clinical observation, crosstalk between germline mutation and somatic mutation, and shared biological pathways. Consequently, by utilizing systematic drug-repositioning approaches, and taking safety issues into consideration, we suggest that oncology drugs have great potential for reuse in the treatment of rare diseases.

Section snippets

Significance of Rare Diseases in Public Health

Rare diseases are usually chronic, serious, and even life-threatening, which creates a burden on society and public health systems [1]. Each rare disease individually affects only small number in the population (<200 000 persons in the USA and <50 000 persons in Europe). For instance, LEOPARD syndrome (LS) is an extremely rare genetic disorder characterized by significant cardiac and skin abnormalities. Only ∼200 patients with LS had been reported worldwide by the year 2008 [2]. However, as a

Translational Insight from Cancer Genomics

Cancer is the most common human genetic disease. Cancers are influenced by multiple factors that include one or more of following: genetic mutations in germline and somatic cells, environmental agents, and the dietary pattern of the host [16]. Thus, the underlying cancer biology is still not fully understood. Many cancers remain mysterious life-threatening and complex diseases [17]. The advent of emerging techniques such as NGS provides an unprecedented solution to identify the genetic basis

Anticancer Drugs for Treating Rare Diseases

The association between rare diseases and cancers raises the possibility that oncology drugs might be employed in the treatment of rare diseases. Encouragingly, several ongoing or completed clinical studies have addressed the potential of oncology drugs in the treatment of rare diseases. For example, nephrogenic systemic fibrosis (NSF) is a rare and serious syndrome that involves fibrosis of skin, joints, eyes, and internal organs. Imatinib, a mixed tyrosine kinase inhibitor developed for the

Repositioning Anticancer Drugs for Rare Disease Treatment

It is encouraging that some efforts have been made to explore the reuse of oncology drugs in rare disease therapy. However, more systematic and sophisticated strategies will be necessary to accelerate the process. Drug repositioning, which addresses new uses for existing drugs, is a well-established paradigm for faster, safer, and cheaper drug development 58, 59, 60. Unlike conventional drug repositioning that has mainly relied on serendipity, modern computational drug-repositioning strategies

Safety of Oncology Drugs for Rare Disease Treatment

Anticancer drugs are inherently toxic because they are designed to kill tumor cells [139]. Approximately 87% of patients experience at least one adverse drug reaction (ADR) with the use of oncology drugs. The experienced ADRs range from nausea and vomiting to severe fatal myelosuppression [140]. About 57% of FDA-approved oncology drugs have boxed warnings (also known as black box warnings), implying that severe ADRs may exist even for approved oncology drugs (Table S3). Most cancer research is

Concluding Remarks and Future Directions

Investigations of cancer genomics data for potential linkage to rare genetic diseases provide a novel approach to rare disease therapy. We have explored emerging links between cancer and rare genetic diseases, and suggest reusing oncology drugs for rare disease therapy. In the near future, novel genomics techniques are likely to provide more extensive data on the specific genetic variations that underlie both cancers and rare diseases, and this will make the association between cancers and rare

Disclaimer Statement

The views presented in this article do not necessarily reflect current or future opinion or policy of the US Food and Drug Administration. Any mention of commercial products is for clarification and not intended as an endorsement.

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