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Journal Article
Review
Emerging molecular-targeted therapies in early-phase clinical trials and preclinical models.
Within the context of modern cooperative group trials, modification of standard cytotoxic chemotherapy has not improved survival in patients with rhabdomyosarcoma (RMS) over the last 30 years. There is need and interest to incorporate novel targeted anticancer agents into the treatment plans for children and adolescents with newly diagnosed RMS; however, targets directly driven by FOXO1 translocation remain elusive, and molecular events driving translocation negative tumors similarly remain ill-defined. Thus, alternate pathways driving the tumors require identification and targeting. Herein, we describe targeted therapies that could be of interest in RMS, but whose inclusion in clinical trials is thus far limited by scientific and regulatory criteria. Sorafenib, pazopanib, crizotinib, TH-302, aurora-kinase inhibitors, and anaplastic lymphoma kinase (ALK)/c-MET inhibitors will be discussed. The current preclinical and clinical data available, as well as limitations and challenges for each, will be outlined.
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