Taxoxifen combined with dasatinib reverses chemo-resistance in breast cancer cells

Researchers from Thomas Jefferson University Hospita,  found that taxoxifen combined with dasatinib, a protein-tyrosine kinase inhibitor, reverses the chemo-resistance caused by cancer-associated fibroblasts in the surrounding tissue by normalizing glucose intake and reducing mitochondrial oxidative stress, the process that fuels the cancer cells. 

In this study, researchers sought to better understand drug resistance by looking at the metabolic basis in an ER (+) cell line and cancer-associated fibroblasts.  Researchers claim that the  resistance to chemotherapeutic agents is a metabolic and stromal phenomenal  and the drug combination had an "antioxidant effect" in these types of cancer cells.  

Researchers showed that ER (+) cancer cells alone responded to tamoxifen but when co-cultured with human fibroblasts had little to no effect. Similarly, dasatinib, a chemotherapy drug used to treat leukemia patients who can no longer benefit from other medications, had no effect on fibroblasts alone or cancer cells. Together, however, the drugs prevented the cancer cells co-cultured with the fibroblasts from using high-energy nutrients from the fibroblasts. Researchers conclude that, 

"The drugs have no effect when they are used alone-it's in unison when they effectively kill the cancer cells in the presence of fibroblasts and combination resulted in nearly 80 percent cell death" 

Ref: http://www.jeffersonhospital.org/News/leukemia-drug-reverses-tamoxifen-resistance-in-breast-cancer-cells.aspx

Sprycel (Dasatinib) for ovarian cancer ?

Dasatinib, is a cancer drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel. Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinases inhibitor approved for use in patients with chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It is also being assessed for use in metastatic melanoma. Its named after Jagabandhu Das, who was a member of the large discovery and development team at Bristol Myers Squibb.

Recently, researchers with UCLA's Jonsson Comprehensive Cancer Center found that Sprycel, significantly inhibited the growth and invasiveness of ovarian cancer cells and also promoted their death. The drug, when paired with a chemotherapy regimen, was even more effective in fighting ovarian cancer in cell lines in which signaling of the Src family kinases, associated with the deadly disease, is activated. The researchers are excited because of the fact that "recent gene expression studies have shown that about one-third of women have ovarian cancers with activated Src pathways", so the drug could potentially help 7,000 ovarian cancer patients every year. Gottfried Konecny (lead researcher) said, it also inhibits the focal adhesion kinase and ephrin receptor, (drug is known to inhibit in many pathways) also associated with ovarian cancer. Though clinical trials are still to be established , its a remarkable achievement. More details .....