Highlights of This Issue

Abstract

In this editorial, Dr. Von Hoff (Editor-In-Chief, Molecular Cancer Therapeutics) introduces a special section of the journal this month that includes 16 commentaries written by authors of some of the best papers published in MCT over the past 10 years. These invited commentaries—“The Best of MCT-10 Years”—help commemorate the journal's 10th anniversary. These papers were selected by the Editors and Editorial Board from the more than 3,000 papers published as having a high ‘patient impact factor'–that is, papers with a lasting impact on research and patient care in the field of cancer therapeutics. Some of these original manuscripts led to drugs currently on the market, others described novel techniques and approaches to drug development.Bortezomib shows remarkable antimyeloma activities; however, the majority of the patients still do not respond or acquire resistance, and biologically based novel treatments are needed. Deacetylases (DAC) modulate both histone and nonhistone protein function, and DAC inhibitors (DACi) have emerged as novel agents against multiple myeloma. Although DACi alone inhibit cell growth and induce apoptosis in multiple myeloma cells, synergistic activity has been observed together with proteasome inhibitors, most likely dependent on a number of mechanisms targeting multiple myeloma cell biology. This combination strategy provides a novel treatment option for the treatment of multiple myeloma patients, including bortezomibrefractory multiple myeloma.Inactivating mutations of the Hedgehog receptor Patched result in activation of the Hedgehog signaling pathway and are the main cause of basal cell carcinoma. Uhmann and colleagues report that calcitriol could be a new option in the treatment of this tumor. By using a Patchedmutant mouse model, the authors show that calcitriol mediates its antitumoral effects by targeting two signaling pathways: firstly, calcitriol inhibits Hedgehog signaling activity and secondly, calcitriol activates the Vitamin D receptor pathway. This dual effect of calcitriol promotes differentiation and inhibits proliferation and growth of basal cell carcinoma, which is the most common tumor in humans.Activation of the phosphoinositide 3-kinase (PI3K) pathway is one of the most frequent genetic events in human cancer. Yuan and colleagues describe the discovery of PF-04691502, a potent inhibitor of two kinases, in the PI3K and mTOR pathways. PF-04691502 potently inhibited tumor cell proliferation and tumor growth in xenograft models of glioblastoma, ovarian cancer, and EGFR inhibitorinsensitive non-small cell lung cancer. PF-04691502 shows promise as an anticancer agent against multiple cancers, including drugresistant tumors, and by targeting two components of the same pathway, may deter acquisition of drug resistance.