| First Author | Uceda-Castro R | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 42 | Pages | eabp9530 |
| PubMed ID | 37851804 | Mgi Jnum | J:341632 |
| Mgi Id | MGI:7542449 | Doi | 10.1126/sciadv.abp9530 |
| Citation | Uceda-Castro R, et al. (2023) BCRP drives intrinsic chemoresistance in chemotherapy-naive breast cancer brain metastasis. Sci Adv 9(42):eabp9530 |
| abstractText | Although initially successful, treatments with chemotherapy often fail because of the recurrence of chemoresistant metastases. Since these tumors develop after treatment, resistance is generally thought to occur in response to chemotherapy. However, alternative mechanisms of intrinsic chemoresistance in the chemotherapy-naive setting may exist but remain poorly understood. Here, we study drug-naive murine breast cancer brain metastases (BCBMs) to identify how cancer cells growing in a secondary site can acquire intrinsic chemoresistance without cytotoxic agent exposure. We demonstrate that drug-naive murine breast cancer cells that form cancer lesions in the brain undergo vascular mimicry and concomitantly express the adenosine 5'-triphosphate-binding cassette transporter breast cancer resistance protein (BCRP), a common marker of brain endothelial cells. We reveal that expression of BCRP by the BCBM tumor cells protects them against doxorubicin and topotecan. We conclude that BCRP overexpression can cause intrinsic chemoresistance in cancer cells growing in metastatic sites without prior chemotherapy exposure. |
