Genomic analysis and preclinical xenograft model development identify potential therapeutic targets for MYOD1 ‐mutant soft‐tissue sarcoma of childhood

2021 ◽  
Author(s):  
Michelle A. Ting ◽  
Jacquelyn Reuther ◽  
Raghu Chandramohan ◽  
Horatiu Voicu ◽  
Ilavarasi Gandhi ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Model Development ◽  
Therapeutic Targets ◽  
Xenograft Model ◽  
Genomic Analysis

A phase I trial of doxorubicin and flavopiridol in soft tissue sarcoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9523-9523 ◽  
Author(s):  
D. R. D’Adamo ◽  
K. Scheu ◽  
S. Singer ◽  
G. K. Schwartz ◽  
R. G. Maki
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase I ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Xenograft Model ◽  
Fixed Dose ◽  
Preclinical Model ◽  
Combination Methods

9523 Background: Flavopiridol, a potent cyclin dependent kinase inhibitor, has been shown in vitro to enhance doxorubicin induced apoptosis. Using the BWH dediffentiated liposarcoma xenograft model we have shown that sequential therapy with doxorubicin (D) followed 1 hour later by flavopiridol (F) is superior to doxorubicin alone (p=0.006). Single agent flavopiridol was also active in this xenograft model, but less so than the combination. Methods: We have commenced an ongoing phase I study of the combination of D and F on the basis of this preclinical data in soft tissue sarcoma with fixed dose D (60 mg/m2), followed 1 hour later by escalating doses of F (40–70 mg/m2) administered over one hour, every 3 weeks. Standard phase I eligibility criteria apply. No prior anthracycline therapy is allowed. At 300 mg/m2 D, dexrazoxane is added to D F. Patients with responsive or stable disease after cumulative D dose of 600mg/m2 can receive single agent flavopiridol. Results: Median characteristics of 7 evaluable patients: age 52 (31–65), KPS 80% (70–90), 3 males / 4 females, 0 prior regimens (range 0–2). The combination has been well-tolerated, with no dose limiting toxicity (DLT) yet. There has been 1 grade 3 bleed in the setting of progressive disease and 1 grade 4 neutropenia without fever. Grade 1 and 2 diarrhea, related to flavopiridol have been observed. Pharmacokinetic (PK) studies are ongoing. We have observed no partial responses (PR). Prolonged stable disease (SD) has been seen in 3 patients for 6, 6 and 11 months. Two patients with SD have liposarcoma. One patient with liposarcoma continues on single agent flavopiridol with stable disease after having reached the prescribed limit of D of 600 mg/m2. Conclusions: The combination of doxorubicin and flavopiridol is safe, with no unexpected toxicities. Disease stabilization in STS has been observed. This appears to be an encouraging combination in liposarcoma and is consistent with our preclinical model. Flavopiridol dose escalation is continuing. No significant financial relationships to disclose.

Abstract 5047: Survival signal pathways as potential therapeutic targets in soft tissue sarcoma cell lines

2011 ◽  
Author(s):  
Jung Woo Han ◽  
Bo Ram Kwon ◽  
Chan Hee Park ◽  
Gui Youn Lee ◽  
Hei-Cheul Jeung ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Cell Lines ◽  
Therapeutic Targets ◽  
Signal Pathways ◽  
Sarcoma Cell ◽  
Survival Signal

Emerging Therapeutic Targets for Soft Tissue Sarcoma

2011 ◽  
Vol 13 (4) ◽  
pp. 350-358 ◽  
Author(s):  
Jason L. Smith ◽  
Richard F. Riedel
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Therapeutic Targets

scholarly journals New Therapeutic Targets in Soft Tissue Sarcoma

2012 ◽  
Vol 19 (3) ◽  
pp. 170-180 ◽  
Author(s):  
Elizabeth G. Demicco ◽  
Robert G. Maki ◽  
Dina C. Lev ◽  
Alexander J. Lazar
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Therapeutic Targets ◽  
New Therapeutic Targets

scholarly journals Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets

2018 ◽  
Vol 19 (S1) ◽  
Author(s):  
Jihyun Kim ◽  
June Hyuk Kim ◽  
Hyun Guy Kang ◽  
Seog Yun Park ◽  
Jung Yeon Yu ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Molecular Characterization ◽  
Therapeutic Targets

scholarly journals Radiation synergizes with antitumor activity of CD13-targeted tissue factor in a HT1080 xenograft model of human soft tissue sarcoma

PLoS ONE ◽  
2020 ◽  
Vol 15 (2) ◽  
pp. e0229271 ◽  
Author(s):  
Caroline Brand ◽  
Burkhard Greve ◽  
Tobias Bölling ◽  
Hans T. Eich ◽  
Normann Willich ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Antitumor Activity ◽  
Tissue Factor ◽  
Xenograft Model ◽  
Human Soft Tissue

Establishment and characterization of a canine soft tissue sarcoma patient-derived xenograft model

2016 ◽  
Vol 15 (3) ◽  
pp. 754-763
Author(s):  
J. P. Frazier ◽  
E. Beirne ◽  
S. H. Ditzler ◽  
I. Tretyak ◽  
J. R. Casalini ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Xenograft Model ◽  
Soft Tissue Sarcoma Patient ◽  
Patient Derived Xenograft ◽  
Sarcoma Patient
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