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  • Review Article
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Targeted therapy in rare cancers—adopting the orphans

Nature Reviews Clinical Oncology volume 9, pages 631–642 (2012)Cite this article

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Abstract

Designation of a rare 'orphan' disease is usually conferred by a prevalence of one in 1,500 to 2,500 individuals. Increasingly, orphan diseases are also being defined by their molecular fingerprints. Rare diseases are uniquely challenging from a therapeutic standpoint; it is critical to modify clinical study design of treatments for orphan disorders as well as for the increasingly smaller molecular subsets within frequently occurring cancers. In spite of the immense challenges associated with developing a treatment for a rare disorder, some of the most groundbreaking therapeutic discoveries have been made in orphan malignancies. This situation may be because a limited number of driver molecular aberrations occur in rare disorders, which can be targeted by agents. Here, we describe drug-class examples of targeted therapies for orphan diseases, with particular emphasis on malignancies or tumour-prone nonmalignant conditions, as well as potential therapeutic strategies that can be adopted to treat these orphan conditions.

Key Points

  • The terms 'rare disorder' and 'orphan disease' are often used interchangeably

  • Dramatic success in treating some orphan cancers is owing to identifying a main driver of malignant transformation

  • By contrast, slow progress has been seen in drug development for the most-common tumours

  • Identification of molecular aberrations may turn common tumours into a collection of orphan diseases

  • The therapeutic paradigm is changing from 'one size fits all' to personalized targeted treatment

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Figure 1: Targeted therapy for orphan diseases.
Figure 2: Distribution of types of sarcoma in childhood.
Figure 3: Cancer in the molecular era.
Figure 4: The elusive equation of targeted therapy: 'the right patient, the right disease, the right drug' in a Venn diagram.
Figure 5

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Acknowledgements

The authors would like to thank Joann Aaron, a medical editor funded by our department, for her editorial assistance.

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  1. Department of Investigational Cancer Therapeutics (Phase I Program), University of Texas, MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, 77030-4009, TX, USA

    Javier Munoz & Razelle Kurzrock

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  1. Javier Munoz
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J. Munoz researched data for the article. Both authors made a substantial contribution to the discussion of the content, to writing the manuscript and to editing prior to submission.

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Correspondence to Javier Munoz.

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Competing interests

R. Kurzrock has received research funding or honoraria from AstraZeneca, Centocor, Genetics, Genentech, Hoffman LaRoche, Novartis, Pfizer, and Wyeth. J. Munoz declares no competing interests.

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Munoz, J., Kurzrock, R. Targeted therapy in rare cancers—adopting the orphans. Nat Rev Clin Oncol 9, 631–642 (2012). https://doi.org/10.1038/nrclinonc.2012.160

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