Tailored approaches to rare sarcomas: current challenges and future prospects

ABSTRACT

Introduction: Based on the emergence of new molecular diagnostic tools over the past decade, sarcomas now gather a variety of rare histological and molecular subtypes. Here, the authors summarize characteristics of the rarest subtypes (<1%), and detail current and future tailored therapeutic options.

Areas covered: This review outlines the current and future approaches towards the tailored therapeutic of rare sarcomas, the gaps in our knowledge and how new molecular tools can be used for drug discovery. A literature search was performed using PubMed. Recent clinical trials testing targeted therapies for sarcomas are reviewed in detail.

Expert commentary: The outcome of metastatic sarcoma patients has remained poor for several decades, highlighting the need for a novel research approach. Nevertheless, this strategy remains challenging because of the rarity of each molecular subtype. Results are promising but generalization of this approach will require new trial designs and a softening of the corresponding regulatory framework. Furthermore, initiatives in obtaining tumor samples to further explore the genetic and immunological profile of sarcomas will be essential in order to further identify novel pathways and targets to exploit.

KEYWORDS:

• Sarcoma
• rare disease
• specific genetic alteration
• complex genomics
• targeted therapies

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. A peer reviewer for this manuscript serves as institutional PI for the STARTRK-2 study (entrectinib) and has served on an advisory board for LOXO (larotrectinib) and Ignyta (entrectinib). Both are mentioned in the manuscript. The reviewer also serves as institutional PI for the AADi ABI-009 study in PEComa.

Additional information

Funding

This paper was not funded.