Targeted Therapy-based Combination Treatment in Rhabdomyosarcoma

Targeted therapies have revolutionized cancer treatment; however, progress lags behind in alveolar (ARMS) and embryonal rhabdomyosarcoma (ERMS), a soft-tissue sarcoma mainly occurring at pediatric and young adult age. Insulin-like growth factor 1 receptor (IGF1R)-directed targeted therapy is one of...

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Bibliographic Details
Published in:Molecular cancer therapeutics 2018-07, Vol.17 (7), p.1365-1380
Main Authors: van Erp, Anke E M, Versleijen-Jonkers, Yvonne M H, van der Graaf, Winette T A, Fleuren, Emmy D G
Format: Article
Language:English
Subjects:
Alveoli
Apoptosis
Cancer
Cancer therapies
Cell fusion
Chemotherapy
Deoxyribonucleic acid
DNA
DNA damage
Hedgehog protein
Insulin
Kinases
Medical treatment
Proteins
Regulators
Rhabdomyosarcoma
Sarcoma
Signal transduction
Signaling
Tyrosine
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Summary:Targeted therapies have revolutionized cancer treatment; however, progress lags behind in alveolar (ARMS) and embryonal rhabdomyosarcoma (ERMS), a soft-tissue sarcoma mainly occurring at pediatric and young adult age. Insulin-like growth factor 1 receptor (IGF1R)-directed targeted therapy is one of the few single-agent treatments with clinical activity in these diseases. However, clinical effects only occur in a small subset of patients and are often of short duration due to treatment resistance. Rational selection of combination treatments of either multiple targeted therapies or targeted therapies with chemotherapy could hypothetically circumvent treatment resistance mechanisms and enhance clinical efficacy. Simultaneous targeting of distinct mechanisms might be of particular interest in this regard, as this affects multiple hallmarks of cancer at once. To determine the most promising and clinically relevant targeted therapy-based combination treatments for ARMS and ERMS, we provide an extensive overview of preclinical and (early) clinical data concerning a variety of targeted therapy-based combination treatments. We concentrated on the most common classes of targeted therapies investigated in rhabdomyosarcoma to date, including those directed against receptor tyrosine kinases and associated downstream signaling pathways, the Hedgehog signaling pathway, apoptosis pathway, DNA damage response, cell-cycle regulators, oncogenic fusion proteins, and epigenetic modifiers. .
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.mct-17-1131