Current Cancer Drug Targets aims to cover all the latest and outstanding developments in full spectrum of cancer drug discovery and development, including but not limited to cellular and molecular biology, genomics, proteomics, metabolomics, medicinal chemistry, pharmacology, toxicology, and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters/commentary/perspectives, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel drug targets for human anticancer drug discovery continues to grow, this journal has become essential reading for all biomedical and pharmaceutical scientists involved in drug discovery and development. Its scope covers publications related to prevention, diagnosis and treatment of all types of human cancers in various of basic and translational researches, including cancer etiology, signal transduction, biomarker, chemotherapy, hormone therapy, gene therapy, immunotherapy, radiotherapy, immunotherapy and combination therapy, stem cell, tumor environment, metabolism emphasizing on advanced mechanistic investigations.
Joanna Bielańska, Javier Hernández‐Losa, Mireia Pérez-Verdaguer, Teresa Moliné, Rosa Somoza, Santiago Ramón y Cajal, Enric Condom, Joan Carles Ferreres, Antônio Felipe
Peter S. Goedegebuure, Jonathan B. Mitchem, Matthew R. Porembka, Marcus Tan, Brian A. Belt, Andrea Wang‐Gillam, William E. Gillanders, William G. Hawkins, David C. Linehan
Jackee Sanchez, Trever R. Carter, Mark S. Cohen, Brian S. J. Blagg
The 90-kDa heat shock protein (Hsp90) is a molecular chaperone that ensures cellular proteostasis by maintaining the folding, stabilization, activation, and degradation of over 400 client proteins. Hsp90 is not only critical for routine protein maintenance in healthy cells, but also during states of cellular stress, such as cancer and neurodegenerative diseases. Due to its ability to affect phosphorylation of numerous client proteins, inhibition of Hsp90 has been an attractive anticancer approach since the early 1990’s, when researchers identified a druggable target on the amino terminus of Hsp90 for a variety of cancers. Since then, 17 Hsp90 inhibitors that target the chaperone’s Nterminal domain, have entered clinical trials. None, however, have been approved thus far by the FDA as a cancer monotherapy. In these trials, a major limitation observed with Hsp90 inhibition at the N-terminal domain was dose-limiting toxicities and relatively poor pharmacokinetic profiles. Despite this, preclinical and clinical research continues to show that Hsp90 inhibitors effectively target cancer cell death and decrease tumor progression supporting the rationale for the development of novel Hsp90 inhibitors. Here, we present an in-depth overview of the Hsp90 inhibitors used in clinical trials. Finally, we present current shifts in the field related to targeting the carboxy-terminal domain of Hsp90 as well as to the development of isoform-selective inhibitors as a means to bypass the pitfalls of current Hsp90 inhibitors and improve clinical trial outcomes.