Targeted agents for sarcoma: is individualized therapy possible in such a diverse tumor type?

Abstract:

:A wide variety of cytogenetic abnormalities and molecular pathways have been implicated in the pathogenesis of sarcoma, and significant progress has been made in the past decade toward identifying potential therapeutic targets. However, apart from gastrointestinal stromal tumors (GISTs) and dermatofibrosarcoma protuberans (DFSP), little progress has been made toward translating that knowledge into effective therapeutic strategies. The identification of activating KIT mutations in the majority of GISTs was a defining moment that led to the first effective targeted therapy for sarcoma, and the subsequent use of imatinib mesylate has revolutionized the treatment of GISTs. Beyond imatinib, the most promising agents to date--and the agents most extensively studied--are the multitargeted tyrosine kinase inhibitors. Several other classes of agents have also shown some activity in soft tissue sarcomas, including mammalian target of rapamycin inhibitors, inhibitors of growth factor receptors, histone deacetylase inhibitors, agents that modulate the p53 pathway, inhibitors of molecular chaperone proteins (eg, heat shock protein 90 [Hsp90]), and other signal transduction inhibitors. Despite a large number of completed and ongoing phase II studies, few agents have moved to phase III testing, and much work remains to be done to fully validate the identified targets and determine the optimal treatment strategy. Ongoing studies are exploring a wide range of combination strategies. This review will highlight some of the emerging targeted therapies that appear to hold promise and may eventually contribute to improved systemic therapy for sarcoma.

journal_name

Semin Oncol

journal_title

Seminars in oncology

authors

Riedel RF

doi

10.1053/j.seminoncol.2011.09.003

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

S30-42

eissn

0093-7754

issn

1532-8708

pii

S0093-7754(11)00235-1

journal_volume

38 Suppl 3

pub_type

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