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Integrative genomic profiling of human prostate cancer.
Annotation of prostate cancer genomes provides a foundation for discoveries that can impact disease understanding and treatment. Concordant assessment of DNA copy number, mRNA expression, and focused… Expand
The phosphatidylinositol 3-Kinase–AKT pathway in human cancer
One signal that is overactivated in a wide range of tumour types is the production of a phospholipid, phosphatidylinositol (3,4,5) trisphosphate, by phosphatidylinositol 3-kinase (PI3K). This lipid… Expand
Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.
BACKGROUND BCR-ABL is a constitutively activated tyrosine kinase that causes chronic myeloid leukemia (CML). Since tyrosine kinase activity is essential to the transforming function of BCR-ABL, an… Expand
Molecular determinants of resistance to antiandrogen therapy
Using microarray-based profiling of isogenic prostate cancer xenograft models, we found that a modest increase in androgen receptor mRNA was the only change consistently associated with the… Expand
Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification
Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. Through… Expand
Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate Cancer
A Second Act for Antiandrogens Men with advanced prostate cancer are often treated with antiandrogens; drugs that inhibit the activity of male hormones, such as testosterone, that help drive tumor… Expand
Integrative Clinical Genomics of Advanced Prostate Cancer
Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct… Expand
Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.
BACKGROUND BCR-ABL, a constitutively activated tyrosine kinase, is the product of the Philadelphia chromosome. This enzyme is present in virtually all cases of chronic myeloid leukemia (CML)… Expand
Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor
Resistance to the ABL kinase inhibitor imatinib (STI571 or Gleevec) in chronic myeloid leukemia (CML) occurs through selection for tumor cells harboring BCR-ABL kinase domain point mutations that… Expand
Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia.
Through sequencing analysis of blood or bone marrow samples from patients with chronic myeloid leukemia, we identified BCR-ABL kinase domain mutations in 29 of 32 patients whose disease relapsed… Expand