A precision medicine approach to metabolic therapy for breast cancer in mice.
Commun Biol
; 5(1): 478, 2022 05 20.
Article
en En
| MEDLINE
| ID: mdl-35595952
ABSTRACT
Increasing evidence highlights approaches targeting metabolism as potential adjuvants to cancer therapy. Sodium-glucose transport protein 2 (SGLT2) inhibitors are the newest class of antihyperglycemic drugs. To our knowledge, SGLT2 inhibitors have not been applied in the neoadjuvant setting as a precision medicine approach for this devastating disease. Here, we treat lean breast tumor-bearing mice with the SGLT2 inhibitor dapagliflozin as monotherapy and in combination with paclitaxel chemotherapy. We show that dapagliflozin enhances the efficacy of paclitaxel, reducing tumor glucose uptake and prolonging survival. Further, the ability of dapagliflozin to enhance the efficacy of chemotherapy correlates with its effect to reduce circulating insulin in some but not all breast tumors. Our data suggest a genetic signature for breast tumors more likely to respond to dapagliflozin in combination with paclitaxel. In the current study, tumors driven by mutations upstream of canonical insulin signaling pathways responded to this combined treatment, whereas tumors driven by mutations downstream of canonical insulin signaling did not. These data demonstrate that dapagliflozin enhances the response to chemotherapy in mice with breast cancer and suggest that patients with driver mutations upstream of canonical insulin signaling may be most likely to benefit from this neoadjuvant approach.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Diabetes Mellitus Tipo 2
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Inhibidores del Cotransportador de Sodio-Glucosa 2
Límite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Commun Biol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos