However, retrospective clinicopathologic study found that none of these molecular markers were pre dictive of response selleck to single agent taxane chemotherapy in patients with metastatic breast cancer. We and others have previously found that taxol could induce the unfolded protein response. GRP78 is a multi functional protein involved in the unfolded protein response, chemoresistance, cell proliferation and angio genesis. Abrogation of GRP78 induction sensitizes breast cancer cells to taxol by potentiating the activation of pro apoptotic signal such as JNK phosphorylation and caspase cleavage. Identification of sensitizers for taxol is expected to improve the efficacy of taxol in treating human Inhibitors,Modulators,Libraries tumors.

17 Allylamino 17 demethoxygeldanamycin inhibits Hsp90, a molecular chaperone that is important for the posttranslational folding and stability of some kinases, which are considered important targets for can cer therapy. 17 AAG, by virtue of its effects on multiple signal transduction pathways, may therefore overcome resistance Inhibitors,Modulators,Libraries to molecular targeted therapy. Also, previous studies suggested that there may be additional potential for its use in combination with conventional agents because some of the pathways inhibited by 17 AAG are also implicated in cytotoxic drug resistance. 17 AAG may sensitize a subset of ovarian cancer to pacli taxel, particularly those tumors in which resistance is driven by Hsp90 clients such as ERBB2 and or p Akt. Since GRP78 is involved in taxol response, it may be another heat shock protein that can be targeted to improve the efficacy of taxol.

The use of a non toxic modulator to enhance the anti tumor activity is invaluable in improving the Inhibitors,Modulators,Libraries outcome of patients with cancer. Green tea has been reported to have Inhibitors,Modulators,Libraries useful Inhibitors,Modulators,Libraries pharmacological effects such as inhibition of carcinogenesis, chemoprevention of cancer, and antioxi dative effect. EGCG and flavonoids have 231 . The tumor suppressing rate for EGCG in combination with tamoxifen reached 80%, while EGCG alone inhibited tumor growth by 35%. EGCG also synergistically enhanced the inhibitory effects of sulindac or tamoxifen on human lung cancer cells. In our study, when given at a similar dose, EGCG alone did not inhibit 4T1 breast tumor growth. EGCG in combi nation with taxol resulted in a decrease in tumor weight by 47%, whereas taxol alone inhibited tumor growth by 22. 5%. In addition, the lung metastasis in mice treated with EGCG in combination with taxol was less than that in mice treated with vehicle or taxol alone, while inhibitory effects on the doxorubicin efflux from Ehrlich ascites carcinoma cells. Oral administration of green tea can enhance the inhibitory effects of doxorubi cin on Ehrlich ascites selleckchem MEK162 carcinoma in tumor bearing mice.