Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Expression of FGFRs in WDLPS/DDLPS Patients and Prognostic Impact
2.2. FGFR Targeting in a Patient with Refractory DDLPS
2.3. Involvement of the FGF/FGFR Signaling Pathway in LPS Tumorigenesis
2.4. Dual Targeting of FGFR and MDM2 in WDLPS/DDLPS Cell Lines
2.5. Dual Targeting of FGFR and MDM2 In Vivo
3. Discussion
4. Materials and Methods
4.1. Patients Population
4.2. Analysis of FGFRs Protein Expression in Clinical Samples
4.3. Cell Lines and Culture Conditions
4.4. Real-Time Quantitative Polymerase Chain Reaction (qRT-PCR) Analysis
4.5. Drugs
4.6. Drug Synergy Assays
4.7. Cell Viability, Cell Apoptosis, and Cell Cycle Assays
4.8. Clonogenic Cell Survival Assay
4.9. Western Blotting
4.10. Animal Studies
4.11. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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FGFR1 and FGFR4 Expression | All LPS (n = 418) | WDLPS (n = 127) | DDLPS (n = 291) |
---|---|---|---|
FGFR1 expression | |||
<50 | 304 (73%) | 113 (89%) | 191 (66%) |
≥50 * | 114 (27%) | 14 (11%) | 100 (34%) |
FGFR4 expression | |||
<5 ≥5 * | 307 (73%) 111 (27%) | 109 (86%) 18 (14%) | 198 (68%) 93 (32%) |
FGFR1 and FGFR4 status | |||
FGFR1 < 50 and FGFR4 < 5 | 237 (57%) | 100 (79%) | 137 (47%) |
FGFR1 < 50 and FGFR4 ≥ 5 | 67 (16%) | 13 (10%) | 54 (19%) |
FGFR1 ≥ 50 and FGFR4 < 5 | 70 (17%) | 9 (7%) | 61 (21%) |
FGFR1 ≥ 50 and FGFR4 ≥ 5 § | 44 (11%) | 5 (4%) | 39 (13%) |
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Dadone-Montaudié, B.; Laroche-Clary, A.; Mongis, A.; Chamorey, E.; Di Mauro, I.; Chaire, V.; Finetti, P.; Schiappa, R.; Le Loarer, F.; Birtwisle-Peyrottes, I.; et al. Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting. Cancers 2020, 12, 3058. https://doi.org/10.3390/cancers12103058
Dadone-Montaudié B, Laroche-Clary A, Mongis A, Chamorey E, Di Mauro I, Chaire V, Finetti P, Schiappa R, Le Loarer F, Birtwisle-Peyrottes I, et al. Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting. Cancers. 2020; 12(10):3058. https://doi.org/10.3390/cancers12103058
Chicago/Turabian StyleDadone-Montaudié, Bérengère, Audrey Laroche-Clary, Aline Mongis, Emmanuel Chamorey, Ilaria Di Mauro, Vanessa Chaire, Pascal Finetti, Renaud Schiappa, François Le Loarer, Isabelle Birtwisle-Peyrottes, and et al. 2020. "Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting" Cancers 12, no. 10: 3058. https://doi.org/10.3390/cancers12103058