Articles in 2013

The anticancer efficacy of conventional chemotherapies seems to be due, in part, to augmentation of the host immune reactivity. However, a new study reveals that two common chemotherapeutic agents, gemcitabine and 5-fluorouracil, can also activate immune regulatory cells, which stimulates the emergence of protumorigenic cytokines via inflammasome pathways, limiting the antitumor efficacy of the drugs (pages 57–64).

Production of the amyloid-β peptide in Alzheimer's disease by the γ-secretase complex can be regulated by certain G protein–coupled receptors. This regulation seems to be mediated by β-arrestin-2, whose expression was found to be elevated in Alzheimer's disease brains (pages 43–49).

A recent court ruling that favored freedom of speech over the authority of the US Food and Drug Administration (FDA) to regulate off-label drug promotion may have profound implications for the way drugs are marketed and, ultimately, for patients' interests.

Distinct roadblocks prevent translating basic findings in viral pathogenesis into therapies and implementing potential solutions in the clinic. An ongoing partnership between the Volkswagen Foundation and Nature Medicine resulted in an interactive meeting in 2012, as part of the “Herrenhausen Symposia” series. Current challenges for various fields of viral research were recognized and discussed with a goal in mind—to identify solutions and propose an agenda to address the translational barriers. Here, some of the researchers who participated at the meeting provide a concise outlook at the most pressing unmet research and clinical needs, identifying these key obstacles is a necessary step towards the prevention and cure of human viral diseases.

The term 'mesenchymal stem cells' is widely used, yet the capabilities and characteristics of these postnatal bone marrow stem cells still warrant further examination. A further understanding and clarification of the true potential of these mesenchymal stem cells is crucial for their appropriate exploitation in the clinic.

Inhibition of prosurvival proteins of the BCL family is a promising anticancer strategy; however, the similarities between the family members make the development of specific agents difficult. Current compounds have been designed to target BCL-2, which is frequently elevated in tumors and is an important prosurvival factor, but also inhibit BCL-X_L, which is required for the survival of platelets; thus, thrombocytopenia is a limiting toxic effect in patients. The authors have engineered anti-BCL drugs to generate a more BCL-2–specific compound that has less affinity for BCL-X_L and, therefore, reduced platelet toxicity. The compound is effective in several tumor models in vivo and had reduced toxicity in three patients with refractory leukemia, showing a promising activity and safety profile to refine and improve proapoptotic therapy in cancer.

TRIP-Br2–null mice are resistant to obesity and insulin resistance and have higher energy expenditure because of increased thermogenesis and oxidative metabolism. As expression of this transcriptional regulator is elevated in fat from obese humans, TRIP-Br2 might be a new therapeutic target against insulin resistance and hyperlipidemia.

RNA editing provides epigenetic diversity and is thought to be decreased in cancer. However, this report describes a phenomenon of increased RNA editing associated with malignancy in human liver tumors. The increased editing of AZIN1 is facilitated by the correlative increase in the editing enzyme ADAR1 and induces an amino acid change that leads to subcellular relocalization, increased stability and affinity for antizyme. This effect impairs antizyme's function and increases the stability of its target oncoproteins, providing protumorigenic functions. The hyperediting of AZIN1 is a protumorigenic event in liver cancer pathogenesis.