The Development of Novel Treatment Strategies for Rhabdomyosarcoma

TL;DR

This review discusses new treatment strategies for rhabdomyosarcoma, focusing on molecular targets and risk-based approaches to improve outcomes.

Contribution

The paper provides an updated overview of novel treatment strategies and molecular targets for rhabdomyosarcoma.

Findings

Lower doses of alkylating agents are being studied to reduce toxicity in low-risk patients.

New drugs and inhibitors are being tested for intermediate- to high-risk patients.

Molecular targets like RAS-signaling pathway and fusion genes are being evaluated for high-risk and metastatic cases.

Abstract

In the review, the epidemiology, prognostic factors and recent treatment strategies of rhabdomyosarcoma are summarized. Moreover, potential molecular targets under investigation and the challenges are also discussed.

Rhabdomyosarcoma is a small round-cell soft tissue tumor that occurs mainly in pediatric and adolescent/young adult (AYA) patients but also rarely in adults. Multidisciplinary treatments including multidrug therapy and local therapy (surgery and/or radiation) are the current standard of care, and treatment strategies are determined according to the estimated risk based on the patient’s age, site of onset, and histologic type, as well as the disease stage. New treatment developments in recent years have been based on risk; lower cumulative doses of alkylating agents to reduce late toxicity for low-risk patients are being studied, and long-term maintenance therapy or the addition of new drugs inhibitors to standard multidisciplinary therapy for intermediate- to high-risk patients have been investigated. For high-risk and metastatic patients, novel molecular targeted drug candidates are being evaluated. The target candidates for rhabdomyosarcoma have included the RAS-signaling pathway, ALK, NTRK, FGFR, and MSI-High. In addition, fusion genes (e.g., PAX3/7-FOXO1), which play an important role in diagnostic and prognostic factors, are also being investigated as potential therapeutic targets as their underlying backgrounds are gradually becoming clear. This review summarizes the overall picture of the development of novel therapies for rhabdomyosarcoma and discusses the direction that should be taken in the future.

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