May 29, 2015
Safety and clinical activity of MEDI4736, an anti-programmed cell death-ligand 1 (PD-L1) antibody, in patients with non-small cell lung cancer (NSCLC)
N. A. Rizvi, J. R. Brahmer, S.-H. I. Ou, N. H. Segal, S. Khleif, W.-J. Hwu, M. Gutierrez, P. Schoffski, O. Hamid, J. Weiss, J. Lutzky, M. Maio, J. J. Nemunaitis, D. Jaeger, A. S. Balmanoukian, M. Rebelatto, K. Steele, X. Li, J. A. Blake-Haskins, S. J. Antonia J Clin Oncol 33, 2015 (suppl; abstr 8032)
Background: MEDI4736 (M) is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity. PD-L1 is expressed in NSCLC tumors and may be associated with response to anti-PD-L1 treatment. This ongoing Phase 1/2, multicenter, open-label study (NCT01693562) evaluates the safety and clinical activity...
May 27, 2015
MERIT40 Is an Akt Substrate that Promotes Resolution of DNA Damage Induced by Chemotherapy
Brown KK, Montaser-Kouhsari L, Beck AH, Toker A , Cell Rep , DOI: 10.1016/j.celrep.2015.05.004
Resistance to cytotoxic chemotherapy drugs, including doxorubicin, is a significant obstacle to the effective treatment of breast cancer. Here, we have identified a mechanism by which the PI3K/Akt pathway mediates resistance to doxorubicin. In addition to inducing DNA damage, doxorubicin triggers sustained activation of Akt signaling in breast cancer cells....
May 26, 2015
Contrast-Enhanced Ultrasound with Perflubutane in the Assessment of Anti-Angiogenic Effects: Early Prediction of the Anticancer Activity of Bevacizumab in a Mouse Xenografted Model
R. Watanabe, T. Munemasa, M. Matsumura , ScienceDirect , DOI: 10.1016/j.ultrasmedbio.2015.04.018
To investigate the feasibility of contrast-enhanced ultrasound (CEUS) with perflubutane for evaluating anti-angiogenic effects, we assessed the contrast enhancement of mice xenograft treated with bevacizumab. SJSA-1 implanted mice were imaged before and 2, 6, 9 and 13 d after initiation of bevacizumab or saline treatment. Intra-tumoral perfusion areas were quantified...
May 13, 2015
Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-RasG12V-induced lung cancer by induction of telomeric DNA damage
M. García‐Beccaria, P. Martínez, M. Méndez‐Pertuz, S. Martínez, C. Blanco‐Aparicio, M. Cañamero, F. Mulero, C. Ambrogio, J. M. Flores, D. Megias, M. Barbacid, J. Pastor, M. A. Blasco , EMBO Molecular Medicine , DOI: 10.15252/emmm.201404497
Telomeres are considered anti-cancer targets, as telomere maintenance above a minimum length is necessary for cancer growth. Telomerase abrogation in cancer-prone mouse models, however, only decreased tumor growth after several mouse generations when telomeres reach a critically short length, and this effect was lost upon p53 mutation. Here, we address...
May 11, 2015
Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in Patients With Refractory Solid Tumors
K. Do, D. Wilsker, J. Ji, J. Zlott, T. Freshwater, R. J. Kinders, J. Collins, A. P. Chen, J. H. Doroshow, S. Kummar , Journal of Clinical Oncology , DOI: 10.1200/JCO.2014.60.4009
Purpose: Wee1 tyrosine kinase phosphorylates and inactivates cyclin-dependent kinase (Cdk) ½ in response to DNA damage. AZD1775 is a first-in-class inhibitor of Wee1 kinase with single-agent anti tumor activity in preclinical models. We conducted a phase I study of single-agent AZD1775 in adult patients with refractory solid tumors to determine...