Our research goals have been to (1) understand the molecular basis of acquired drug resistance (2) comprehend how/why these changes occur;(3) search for them in clinical samples and (4) devise strategies to reduce or prevent their occurrence. Our efforts are increasingly directed at understanding how normal tissue might be affected by these agents and the extent to which they might or might not be protected by drug transporters such as P-glycoprotein and the half-transporter, ABCG2 We have also been investigating the role of drug transporters in affording the brain protection from chemotherapeutic agents. Driven in part by the recognition that as we develop more and more agents to be administered orally, we are developing agents that are likely to bypass the mechanisms that protect the brain and confer its status as a sanctuary, since many of the same transporters that protect line the GI tract, and drugs must be designed to bypass them if they are to be administered orally. We are conducting studies to hopefully understand the mechanisms that protect the brain and what might be the consequences of bypassing these barriers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIASC006732-23
Application #
8350051
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
23
Fiscal Year
2011
Total Cost
$469,331
Indirect Cost
Name
National Cancer Institute Division of Clinical Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Blagoev, Krastan B; Wilkerson, Julia; Stein, Wilfred D et al. (2013) Sunitinib does not accelerate tumor growth in patients with metastatic renal cell carcinoma. Cell Rep 3:277-81
Amiri-Kordestani, Laleh; Fojo, Tito (2012) Why do phase III clinical trials in oncology fail so often? J Natl Cancer Inst 104:568-9
Stein, Wilfred D; Wilkerson, Julia; Kim, Sindy T et al. (2012) Analyzing the pivotal trial that compared sunitinib and IFN-? in renal cell carcinoma, using a method that assesses tumor regression and growth. Clin Cancer Res 18:2374-81
Kelly, Ronan J; Robey, Robert W; Chen, Clara C et al. (2012) A pharmacodynamic study of the P-glycoprotein antagonist CBT-1® in combination with paclitaxel in solid tumors. Oncologist 17:512
Amiri-Kordestani, Laleh; Basseville, Agnes; Kurdziel, Karen et al. (2012) Targeting MDR in breast and lung cancer: discriminating its potential importance from the failure of drug resistance reversal studies. Drug Resist Updat 15:50-61
Blagoev, Krastan B; Wilkerson, Julia; Fojo, Tito (2012) Hazard ratios in cancer clinical trials--a primer. Nat Rev Clin Oncol 9:178-83
Fojo, Tito; Amiri-Kordestani, Laleh; Bates, Susan E (2011) Potential pitfalls of crossover and thoughts on iniparib in triple-negative breast cancer. J Natl Cancer Inst 103:1738-40
Kelly, Ronan J; Draper, Deborah; Chen, Clara C et al. (2011) A pharmacodynamic study of docetaxel in combination with the P-glycoprotein antagonist tariquidar (XR9576) in patients with lung, ovarian, and cervical cancer. Clin Cancer Res 17:569-80
Piekarz, Richard L; Frye, Robin; Prince, H Miles et al. (2011) Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood 117:5827-34
Stein, Wilfred D; Gulley, James L; Schlom, Jeff et al. (2011) Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy. Clin Cancer Res 17:907-17

Showing the most recent 10 out of 20 publications