Cabozantinib and dasatinib synergize to induce tumor regression in non-clear cell renal cell carcinoma.
Cell Rep Med
; 2(5): 100267, 2021 05 18.
Article
em En
| MEDLINE
| ID: mdl-34095877
ABSTRACT
The lack of effective treatment options for advanced non-clear cell renal cell carcinoma (NCCRCC) is a critical unmet clinical need. Applying a high-throughput drug screen to multiple human kidney cancer cells, we identify the combination of the VEGFR-MET inhibitor cabozantinib and the SRC inhibitor dasatinib acts synergistically in cells to markedly reduce cell viability. Importantly, the combination is well tolerated and causes tumor regression in vivo. Transcriptional and phosphoproteomic profiling reveals that the combination converges to downregulate the MAPK-ERK signaling pathway, a result not predicted by single-agent analysis alone. Correspondingly, the addition of a MEK inhibitor synergizes with either dasatinib or cabozantinib to increase its efficacy. This study, by using approved, clinically relevant drugs, provides the rationale for the design of effective combination treatments in NCCRCC that can be rapidly translated to the clinic.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Piridinas
/
Carcinoma de Células Renais
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Dasatinibe
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Anilidas
Limite:
Humans
Idioma:
En
Revista:
Cell Rep Med
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos