Lani
08-06-2013, 08:02 PM
few things have been shown to prevent bc spread to the brain or the mets taking hold there.
Dr. Steeg has made this her special field of interest
It is only in an animal model, but the principle (having the Src inhibitor prevent the bc cells from crossing into the brain in the first place and keeping them from taking hold and flourishing seems spot-on.
Cancer Res. 2013 Aug 1. [Epub ahead of print]
Src family kinases as novel therapeutic targets to treat breast cancer brain metastases.
Zhang S, Huang WC, Zhang L, Zhang C, Lowery FJ, Ding Z, Guo H, Wang H, Huang S, Sahin AA, Aldape KD, Steeg PS, Yu D.
Source
Department of Biological Sciences, University of Notre Dame.
Abstract
Despite better control of early stage disease and improved overall survival of patients with breast cancer, the incidence of life-threatening brain metastases continues to increase in some of these patients. Unfortunately, other than palliative treatments there is no effective therapy for this condition. In this study, we reveal a critical role for Src activation in promoting brain metastasis in a preclinical model of breast cancer, and we show how a Src-targeting combinatorial regimen can treat HER2+ brain metastases in this model. We found that Src was hyperactivated in brain-seeking breast cancer cells derived from human cell lines or from patients' brain metastases. Mechanistically, Src activation promoted tumor cell extravasation into the brain parenchyma via permeabilization of the blood-brain barrier. When combined with the EGFR/HER2 dual-targeting drug lapatinib, a Src-targeting combinatorial regimen prevented outgrowth of disseminated breast cancer cells through the induction of cell cycle arrest. More importantly, this combinatorial regimen inhibited the outgrowth of established experimental brain metastases, prolonging the survival of metastases-bearing mice. Our results provide a rationale for clinical evaluation of Src-targeting regimens to treat breast cancer patients suffering from brain metastasis.
PMID: 23913825
Dr. Steeg has made this her special field of interest
It is only in an animal model, but the principle (having the Src inhibitor prevent the bc cells from crossing into the brain in the first place and keeping them from taking hold and flourishing seems spot-on.
Cancer Res. 2013 Aug 1. [Epub ahead of print]
Src family kinases as novel therapeutic targets to treat breast cancer brain metastases.
Zhang S, Huang WC, Zhang L, Zhang C, Lowery FJ, Ding Z, Guo H, Wang H, Huang S, Sahin AA, Aldape KD, Steeg PS, Yu D.
Source
Department of Biological Sciences, University of Notre Dame.
Abstract
Despite better control of early stage disease and improved overall survival of patients with breast cancer, the incidence of life-threatening brain metastases continues to increase in some of these patients. Unfortunately, other than palliative treatments there is no effective therapy for this condition. In this study, we reveal a critical role for Src activation in promoting brain metastasis in a preclinical model of breast cancer, and we show how a Src-targeting combinatorial regimen can treat HER2+ brain metastases in this model. We found that Src was hyperactivated in brain-seeking breast cancer cells derived from human cell lines or from patients' brain metastases. Mechanistically, Src activation promoted tumor cell extravasation into the brain parenchyma via permeabilization of the blood-brain barrier. When combined with the EGFR/HER2 dual-targeting drug lapatinib, a Src-targeting combinatorial regimen prevented outgrowth of disseminated breast cancer cells through the induction of cell cycle arrest. More importantly, this combinatorial regimen inhibited the outgrowth of established experimental brain metastases, prolonging the survival of metastases-bearing mice. Our results provide a rationale for clinical evaluation of Src-targeting regimens to treat breast cancer patients suffering from brain metastasis.
PMID: 23913825