Clin Cancer Res
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The transcription factor Forkhead box M1 (FOXM1) plays important roles in the formation of several human tumors, including pancreatic cancer. However, the molecular mechanisms by which FOXM1 promotes pancreatic tumor epithelial-to-mesenchymal transition (EMT) and metastasis are unknown. ⋯ Our findings demonstrated that FOXM1c contributes to pancreatic cancer development and progression by enhancing uPAR gene transcription, and thus, tumor EMT and metastasis.
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The androgen receptor pathway remains active in men with prostate cancer whose disease has progressed following surgical or medical castration. Orteronel (TAK-700) is an investigational, oral, nonsteroidal, selective, reversible inhibitor of 17,20-lyase, a key enzyme in the production of androgenic hormones. ⋯ 17,20-Lyase inhibition by orteronel was tolerable and results in declines in PSA and testosterone, with evidence of radiographic responses.
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We investigated the incidence of concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements in Chinese patients with non-small cell lung cancer (NSCLC), and assessed responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib in such tumors. ⋯ ALK rearrangements and EGFR mutations could coexist in a small subgroup of NSCLC. Advanced pulmonary adenocarcinomas with such co-alterations could have diverse responses to EGFR-TKIs and crizotinib. Relative phospho-ALK and phospho-EGFR levels could predict the efficacy of EGFR-TKI and crizotinib.
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We report a retrospective exploratory analysis of the association of the research-based prediction analysis of microarray 50 (PAM50) subtype predictor with pathologic complete response (pCR) and event-free survival (EFS) in women enrolled in the NeOAdjuvant Herceptin (NOAH) trial. ⋯ As determined by EFS and pCR, patients with HER2(+)/HER2-E tumors, or HER2(+)/RORP-high tumors, benefit substantially from trastuzumab-based chemotherapy. The clinical value of this genomic test within HER2(+) disease warrants further investigation.
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Trastuzumab emtansine (T-DM1) is a novel HER2-directed antibody-drug conjugate. T-DM1 consists of the potent antimicrotubule agent DM1, linked via a noncleavable linker to the HER2-specific monoclonal antibody trastuzumab. Preclinical studies demonstrate that T-DM1 has dual mechanisms of action: selective delivery of DM1 to the HER2-positive (HER2(+)) tumor cell combined with trastuzumab's activation of antibody-dependent cell-mediated cytotoxicity and inhibition of HER2-mediated signal transduction. ⋯ Alopecia, peripheral neuropathy, and neutropenia are distinctly uncommon. On the basis of its improved efficacy and toxicity compared with capecitabine/lapatinib, T-DM1 should be considered the standard for patients with HER2(+) metastatic breast cancer who have previously progressed on trastuzumab and a taxane. Results from additional randomized studies in metastatic breast cancer are pending, and trials in the (neo)adjuvant setting are being initiated.