Exploiting Tumor Vulnerabilities: Epigenetics, Cancer Metabolism and the mTOR Pathway in the Era of Personalized Medicine.

Exploiting tumor vulnerabilities: epigenetics, cancer metabolism and the mTOR pathway in the era of Personalized Medicine.

Cancer Res. 2013 May 17;
Muñoz-Pinedo C, González-Suárez E, Portela A, Gentilella A, Esteller M

Patient stratification according to drug responses, together with the discovery of novel anti-tumor targets, is leading to a new era of personalized cancer treatments. With the aim of identifying emerging pathways and the challenges faced by clinicians during clinical trials, the IDIBELL Cancer Conference on Personalized Cancer Medicine took place in Barcelona in December 2012. This conference brought together speakers working in different areas of cancer research (epigenetics, metabolism and the mTOR pathway, cell death and the immune system, clinical oncology) to discuss the latest developments in personalized cancer medicine. HubMed – drug


Zinc-L-Carnosine Binds to Molecular Chaperone HSP70 and Inhibits the Chaperone Activity of the Protein.

J Biochem. 2013 May 17;
Haga A, Okamoto T, Yamada S, Kubota T, Sanpei A, Takahashi S, Nakayama M, Nagai M, Otaka M, Miyazaki T, Nunomura W, Grave E, Itoh H

In the present study, we have investigated the specific binding proteins of Zinc-L-Carnosine (Polaprezinc) using Polaprezinc-affinity column chromatography in vitro. A protein having a 70-kDa molecular mass was eluted by the linear gradient of 0-1.0 mM Polaprezinc from the affinity column and the protein was identified as the molecular chaperone HSP70 by immunoblotting.The chaperone activity of HSP70 was completely suppressed by Polaprezinc. The ATPase activity of HSP70 was affected to some extent by the reagent. In the CD spectrum, the secondary structure of HSP70 was changed in the presence of Polaprezinc, i.e., it decreased in the ?-helix. We have determined the Polaprezinc-binding domain of HSP70 by using recombinant HSP70N- and C-domains. Although Polaprezinc could bind to both the N-terminal and the C-terminal of HSP70, the HSP70N-domain has a high affinity to the drug. Regarding the peptide cleavage of the HSP70N- and C-domains with proteinase K, the intact HSP70N still remained in the presence of Polaprezinc. On the other hand, the quantity of the intact C-domain slightly decreased under the same conditions along with the newly digested small peptides appeared. It has been suggested that Polaprezinc binds to HSP70 especially in the N-domains, suppresses the chaperone activity and delays an ATPase activities of HSP70. HubMed – drug