Therapeutic Potential of Targeting the SUMO Pathway in Cancer

The small ubiquitin-like modifier (SUMO) pathway regulates the hallmark properties of cancer cells. Moreover, alterations in activity and in levels of SUMO machinery components have been observed in human cancer. Due to the reversible nature of this post-translational protein modification, the balance between SUMOylation and the removal of SUMO is critical. Early-phase clinical trials are currently evaluating the safety and efficacy of SUMO pathway inhibition in cancer patients. In this comprehensive review, we critically discuss the potential of targeting the SUMO pathway as a therapeutic option for cancer. </p

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

SUMOylation is a dynamic and reversible post-translational modification, characterized more than 20 years ago, that regulates protein function at multiple levels. Key oncoproteins and tumor suppressors are SUMO substrates. In addition to alterations in SUMO pathway activity due to conditions typically present in cancer, such as hypoxia, the SUMO machinery components are deregulated at the genomic level in cancer. The delicate balance between SUMOylation and deSUMOylation is regulated by SENP enzymes possessing SUMO-deconjugation activity. Dysregulation of SUMO machinery components can disrupt the balance of SUMOylation, contributing to the tumorigenesis and drug resistance of various cancers in a context-dependent manner. Many molecular mechanisms relevant to the pathogenesis of specific cancers involve SUMO, highlighting the potential relevance of SUMO machinery components as therapeutic targets. Recent advances in the development of inhibitors targeting SUMOylation and deSUMOylation permit evaluation of the therapeutic potential of targeting the SUMO pathway in cancer. Finally, the first drug inhibiting SUMO pathway, TAK-981, is currently also being evaluated in clinical trials in cancer patients. Intriguingly, the inhibition of SUMOylation may also have the potential to activate the anti-tumor immune response. Here, we comprehensively and systematically review the recent developments in understanding the role of SUMOylation in cancer and specifically focus on elaborating the scientific rationale of targeting the SUMO pathway in different cancers

Fast detection of Noroviruses using a real-time PCR assay and automated sample preparation

<p>Abstract</p> <p>Background</p> <p>Noroviruses (NoV) have become one of the most commonly reported causative agents of large outbreaks of non-bacterial acute gastroenteritis worldwide as well as sporadic gastroenteritis in the community. Currently, reverse transcriptase polymerase chain reaction (RT-PCR) assays have been implemented in NoV diagnosis, but improvements that simplify and standardize sample preparation, amplification, and detection will be further needed. The combination of automated sample preparation and real-time PCR offers such refinements.</p> <p>Methods</p> <p>We have designed a new real-time RT-PCR assay on the LightCycler (LC) with SYBR Green detection and melting curve analysis (T_m) to detect NoV RNA in patient stool samples. The performance of the real-time PCR assay was compared with that obtained in parallel with a commercially available enzyme immunoassay (ELISA) for antigen detection by testing a panel of 52 stool samples. Additionally, in a collaborative study with the Baden-Wuerttemberg State Health office, Stuttgart (Germany) the real-time PCR results were blindly assessed using a previously well-established nested PCR (nPCR) as the reference method, since PCR-based techniques are now considered as the "gold standard" for NoV detection in stool specimens.</p> <p>Results</p> <p>Analysis of 52 clinical stool samples by real-time PCR yielded results that were consistent with reference nPCR results, while marked differences between the two PCR-based methods and antigen ELISA were observed. Our results indicate that PCR-based procedures are more sensitive and specific than antigen ELISA for detecting NoV in stool specimens.</p> <p>Conclusions</p> <p>The combination of automated sample preparation and real-time PCR provided reliable diagnostic results in less time than conventional RT-PCR assays. These benefits make it a valuable tool for routine laboratory practice especially in terms of rapid and appropriate outbreak-control measures in health-care facilities and other settings.</p