| Autor: |
Neta, Moskovits, Idit, Peretz, Eva, Chausky, Ella, Itzhaki, Nofar, Shmuel, Raisa, Meerson, Nataly, Tarasenko, Aleksandr, Kaufman, Amos, Stemmer, Ranny, Yaffe, Avital, Bareket-Samish, Natalia, Edison, Tal, Goldman, Salomon M, Stemmer |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cancer Letters. 536:215665 |
| ISSN: |
0304-3835 |
| Popis: |
The efficacy/safety of combining palbociclib (a CDK4/6 inhibitor) and sunitinib (a multi-targeted receptor tyrosine kinase inhibitor) was evaluated, using patient-derived xenograft (PDX) models. Twenty-three PDX mice models were developed from patients with various solid tumors. The mice were randomized to 4 groups (5-6 mice in each): control/palbociclib (100 mg/kg)/sunitinib (50 mg/kg)/combination. Drugs were administered orally, 5 days/week. In 17/23 PDX models (74%), the combination demonstrated a synergistic inhibitory effect vs the monotherapies ("responder" models) with no unexpected toxicities. In 13/17 responder models, where standard-of-care (SOC) was an additional comparator, the combination was more effective than SOC in 7 models, as effective in 4, and less effective in 2. The mean ± SEM experiment duration in 15/17 responder models (2/17 were excluded due to technical issues) was 86 ± 12 and 31 ± 5 days for the combination and control groups, respectively (p = 0.0002). The effect of the combination was dose-dependent. Cell-viability experiments in A549/MDA-MB-231/HT-29 cell lines and experiments using tumor-derived primary cell spheroids supported the PDX findings. In conclusion, combination of palbociclib and sunitinib exerts a synergistic anti-tumor effect without adding unexpected toxicity. A clinical trial assessing this combination is underway. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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