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Updated: Aug 10, 2026
A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing (Neo)adjuvant Therapies
Published on: July 28, 2020
New emerging drugs in soft tissue sarcoma
Amalia Milano1, Gaetano Apice, Ettore Ferrari
1Istituto Nazionale Tumori, Fondazione G. Pascale, Via M. Semmola, 80131 Napoli, Italy.
Abstract:
Doxorubicin and ifosfamide are the two most active drugs in the treatment of patients with advanced, soft tissue sarcoma (STS) of most histologic subtypes, aside from gastrointestinal stromal tumor (GIST). However, after failure of these drugs, alone or in combination, patients with advanced STS have few therapeutic options and the search for new active drugs is well worth pursuing. ET-743, a DNA minor groove binder, which blocks cell cycle progression in G2/M phase through a p53-independent apoptotic process, represents the most promising among novel compounds in STS, since recently completed phase II trials have consistently shown high survival, in spite of the relatively low incidence of major objective responses. The potential for combination with other active compounds further increases the appeal of ET-743. Imatinib mesylate is being tested also in STS other than GIST, which can overexpress one or more of the tyrosine kinases inhibited by imatinib; however, negative data have recently been presented. Clinical studies with a number of other compounds are ongoing or planned. However, investigators involved in the management of patients with advanced STS are to be increasingly aware of the emergence of new molecular targets and genetic profiles in different histologic subtypes, according to which treatment strategies should be adapted.
Insights
For advanced soft tissue sarcoma (STS) patients, novel therapies like ET-743 show promise after standard drug failure. Research continues for new treatments targeting specific molecular profiles in STS.
Area of Science:
- Medical Oncology
- Pharmacology
- Genetics
Background:
- Doxorubicin and ifosfamide are standard treatments for advanced soft tissue sarcoma (STS), but options are limited after their failure.
- Gastrointestinal stromal tumor (GIST) is an exception, with different therapeutic approaches.
- There is a critical need for novel therapeutic agents for advanced STS.
Purpose of the Study:
- To review the current landscape of treatment options for advanced soft tissue sarcoma (STS).
- To highlight promising novel compounds, particularly ET-743, for STS treatment.
- To emphasize the importance of adapting treatment strategies based on molecular targets and genetic profiles.
Main Methods:
- Review of recent clinical trial data for novel compounds in advanced STS.
- Analysis of the mechanism of action and efficacy of ET-743.
- Discussion of emerging molecular targets and genetic profiles in different STS subtypes.
Main Results:
- ET-743 demonstrates significant survival benefits in phase II trials for advanced STS, despite limited objective response rates.
- Imatinib mesylate has shown negative results in STS beyond GIST.
- Ongoing and planned clinical studies are exploring various other compounds.
Conclusions:
- ET-743 is a promising novel agent for advanced STS, with potential for combination therapies.
- Future treatment strategies for advanced STS should be tailored to specific histologic subtypes and their molecular/genetic profiles.
- Continued research into new molecular targets and therapies is essential for improving outcomes in advanced STS.
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