Peptide-based cancer therapy has been of great interest due to the unique advantages of peptides, such as the low molecular weight, the ability to specifically target tumor cells, easy availability and low toxicity in normal tissues. Therefore, identify and synthesize novel peptides could provide a promising choice to patients with cancer. The antitumor second generation peptide CIGB-552 has been developed as a candidate to cancer treatment. Proteomic and genomic studies have identified the intracellular protein COMMD1 as the specific target of CIGB-552. This peptide penetrates inside tumor cells to induce the proteasomal degradation of RelA, causing the termination of NF-kB signaling. The antitumor activity of CIGB-552 has been validated in vitro in different human cancer cell lines, as well as in vivo in syngeneic and xenograft tumor mouse models and in cancer-bearing dogs. The aim of this review is to present and discuss the experimental data about CIGB-552, its mechanism of action and its therapeutic potential in human chronic diseases. This peptide is already in phase I of clinical trials as antineoplastic drug, but also has possible application to other inflammatory and metabolic conditions.

An increase in pulmonary artery pressure is a common observation in adult mammals exposed to alveolar hypoxia. It is considered a maladaptive response that places an increased workload on the right ventricle. The mechanisms initiating and maintaining the elevated pressure are of considerable interest to understanding pulmonary vascular homeostasis and developing new treatments for pulmonary hypertension. In particular, it would be helpful to discover the key molecules in the integrated vascular response to hypoxia to inform potential drug targets. One strategy is to take advantage of experiments of nature; specifically, to understand the molecular basis for the inter-individual variation in the pulmonary vascular response to acute and chronic hypoxia. This is the motivation for genetic studies in populations and animals adapted to life at high altitudes. To date, these studies highlight the importance of hypoxia-inducible factor 2α (HIF-2α), encoded by EPAS1, and prolyl hydroxylase domain-containing protein 2 (PHD), encoded by EGLN1, and support efforts to pharmacologically manipulate HIF-2 activity as a treatment for pulmonary hypertension.

Many current animal models of heart failure are hampered by intrinsic methodological complexities, while other models yield only a subtle cardiac phenotype even after prolonged in vivo treatments. A new “chemogenetic” animal model of heart failure recapitulates a critical characteristic shared by many disease states that lead to heart failure in humans: an increase in redox stress in the heart. This “chemogenetic” approach exploits a recombinant yeast enzyme that can be dynamically and specifically activated in vivo to generate the reactive oxygen species (ROS) hydrogen peroxide (H2O2) in cardiac myocytes. Redox stress can be rapidly, selectively, and reversibly manipulated by chemogenetic generation of ROS in cardiac myocytes, yielding a new model of dilated cardiomyopathy. Treatment of animals with the angiotensin receptor blocker valsartan promotes recovery of ventricular function and resolution of adverse cardiac remodeling. This Mini-Review discusses in vivo chemogenetic approaches to manipulate and analyze oxidative stress in the heart.