Lani
09-10-2013, 10:08 PM
bc and it is an.......anti-worm drug!!! Seems like much smaller doses may be needed but it is still in the early stages and not yet investigated in humans
Love when drugs already approved prove so helpful(makes it much more likely to be available soon)...now to test it in humans
By the way, about 45% of IBC is her2+ it seems
PLoS One. 2013 Aug 27;8(8):e71508. doi: 10.1371/journal.pone.0071508.
The antihelmintic drug pyrvinium pamoate targets aggressive breast cancer.
Xu W, Lacerda L, Debeb BG, Atkinson RL, Solley TN, Li L, Orton D, McMurray JS, Hang BI, Lee E, Klopp AH, Ueno NT, Reuben JM, Krishnamurthy S, Woodward WA.
Source
Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Abstract
WNT signaling plays a key role in the self-renewal of tumor initiation cells (TICs). In this study, we used pyrvinium pamoate (PP), an FDA-approved antihelmintic drug that inhibits WNT signaling, to test whether pharmacologic inhibition of WNT signaling can specifically target TICs of aggressive breast cancer cells. SUM-149, an inflammatory breast cancer cell line, and SUM-159, a metaplastic basal-type breast cancer cell line, were used in these studies. We found that PP inhibited primary and secondary mammosphere formation of cancer cells at nanomolar concentrations, at least 10 times less than the dose needed to have a toxic effect on cancer cells. A comparable mammosphere formation IC50 dose to that observed in cancer cell lines was obtained using malignant pleural effusion samples from patients with IBC. A decrease in activity of the TIC surrogate aldehyde dehydrogenase was observed in PP-treated cells, and inhibition of WNT signaling by PP was associated with down-regulation of a panel of markers associated with epithelial-mesenchymal transition. In vivo, intratumoral injection was associated with tumor necrosis, and intraperitoneal injection into mice with tumor xenografts caused significant tumor growth delay and a trend toward decreased lung metastasis. In in vitro mammosphere-based and monolayer-based clonogenic assays, we found that PP radiosensitized cells in monolayer culture but not mammosphere culture. These findings suggest WNT signaling inhibition may be a feasible strategy for targeting aggressive breast cancer. Investigation and modification of the bioavailability and toxicity profile of systemic PP are warranted.
PMID: 24013655
Love when drugs already approved prove so helpful(makes it much more likely to be available soon)...now to test it in humans
By the way, about 45% of IBC is her2+ it seems
PLoS One. 2013 Aug 27;8(8):e71508. doi: 10.1371/journal.pone.0071508.
The antihelmintic drug pyrvinium pamoate targets aggressive breast cancer.
Xu W, Lacerda L, Debeb BG, Atkinson RL, Solley TN, Li L, Orton D, McMurray JS, Hang BI, Lee E, Klopp AH, Ueno NT, Reuben JM, Krishnamurthy S, Woodward WA.
Source
Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Abstract
WNT signaling plays a key role in the self-renewal of tumor initiation cells (TICs). In this study, we used pyrvinium pamoate (PP), an FDA-approved antihelmintic drug that inhibits WNT signaling, to test whether pharmacologic inhibition of WNT signaling can specifically target TICs of aggressive breast cancer cells. SUM-149, an inflammatory breast cancer cell line, and SUM-159, a metaplastic basal-type breast cancer cell line, were used in these studies. We found that PP inhibited primary and secondary mammosphere formation of cancer cells at nanomolar concentrations, at least 10 times less than the dose needed to have a toxic effect on cancer cells. A comparable mammosphere formation IC50 dose to that observed in cancer cell lines was obtained using malignant pleural effusion samples from patients with IBC. A decrease in activity of the TIC surrogate aldehyde dehydrogenase was observed in PP-treated cells, and inhibition of WNT signaling by PP was associated with down-regulation of a panel of markers associated with epithelial-mesenchymal transition. In vivo, intratumoral injection was associated with tumor necrosis, and intraperitoneal injection into mice with tumor xenografts caused significant tumor growth delay and a trend toward decreased lung metastasis. In in vitro mammosphere-based and monolayer-based clonogenic assays, we found that PP radiosensitized cells in monolayer culture but not mammosphere culture. These findings suggest WNT signaling inhibition may be a feasible strategy for targeting aggressive breast cancer. Investigation and modification of the bioavailability and toxicity profile of systemic PP are warranted.
PMID: 24013655