Pharmacogenomics of breast cancer targeted therapy: focus on recent patents

Adjuvant endocrine therapy as well as other forms of targeted therapy such as HER2 inhibitors and antiangiogenic agents reduce the risk of recurrence and improve survival among women with hormone receptor positive breast cancer. However, a significant percentage of women who receive targeted therapy as adjuvant or metastatic treatment do not benefit from this therapy, while a number of women who initially respond will eventually develop disease progression and relapse while on therapy. The observed variability in treatment response to targeted breast cancer treatment could be partly explained by pharmacogenomics. This paper reviews evidence on the role of pharmacogenomics of breast targeted therapy focusing on the clinical relevance of genetic variation. In particular, this article reviews the role of pharmacogenomics of tamoxifen, aromatase inhibitors, HER-2 inhibitors and anti-angiogenic agents. In addition, recent patents in the field are presented that provide promising steps in the field of personalized treatment of breast cancer, although future studies are needed for determining the clinical benefit of the proposed inventions. Finally, we present a testable hypothesis to aide the search for biologically meaningful genetic variation Specifically, we suggest the publication of negative results in the field of pharmacogenomics and pharmacoproteomics, will benefit future research in the field.     

Protective effect of salicylates against hydrogen peroxide stress in yeast

Aims:  To investigate the effects of salicylates in Saccharomyces cerevisiae exposed to oxidative stress induced by hydrogen peroxide (H₂O₂).
Methods and Results:  Saccharomyces cerevisiae was cultured through to the postlogarithmic phase of growth. Stress was induced by the addition of 1·5 mmol l⁻¹ H₂O₂ for 1 h, while N-acetyl-l-cysteine (NAC) and glutathione (GSSG) were used as control agents that affect the redox balance. Sodium salicylate, at 0·01–10 mmol l⁻¹or acetylsalicylic acid, at 0·02–2·5 mmol l⁻¹ was administered at various times before hydrogen peroxide stress. Both agents conferred resistance to a subsequent hydrogen peroxide stress, similarly to the induction of the adaptive response observed upon pretreatment with NAC and GSSG. Sodium salicylate was more potent as a short-term, but not as a long-term pretreatment agent, compared to acetylsalicylic acid.
Conclusions:  Pharmacological pretreatment with salicylates resulted in dose related increases in cell survival, indicating the induction of the protective response in yeast.
Significance and Impact of the study:  The possible role of salicylates in the modulation of the hydrogen peroxide stress response in eukaryotic cells address questions on the effects of these commonly used therapeutic agents in a number of disorders exhibiting an oxidative stress component.     

Water Quality Trends in a Coastal Lagoon Impacted by Non-point Source Pollution after Implementation of Protective Measures

Water quality data from two different monitoring periods are used to evaluate the trophic state and effectiveness of various protective measures on the restoration of a eutrophic, coastal Mediterranean lagoon. Main protective measures included elimination of municipal/industrial raw wastewater discharges in the rivers outflowing to the lagoon, sediment/erosion control practices in the lagoon’s drainage basin (i.e., construction of sediment/debris dams and grade control structures, reforestation and ban on livestock grazing), and reduction of fertilizer application quantities as a result of changes in crops. Water quality data include, among others, chlorophyll a, dissolved oxygen and nutrient concentrations, various physicochemical parameters, and transparency, measured during two monitoring periods, i.e., before (1983–84) and after (1998–99) implementation of protective measures. Rainfall depth for the two time periods was also available. Empirical equations were developed, from statistical analyses of the data, relating the water quality parameters during the two monitoring periods. These models help identify water quality trends. Based on the analyses, it seems that measures were effective in reducing sediments transported into the lagoon. However, the lagoon remains eutrophic to hypereutrophic, mostly due to phosphorus released in the water column from bottom sediments. Therefore, future restoration efforts should be directed towards the management of bottom sediments.