Multimodal oncological strategies which combine chemotherapy or radiotherapy with hyperthermia, have a potential of improving the efficacy of the non-surgical methods of cancer treatment. Hyperthermia engages the heat-shock response (HSR) mechanism, the main component of which are heat-shock proteins. Cancer cells have already partially activated HSR, thereby hyperthermia may be more toxic to them relative to normal cells. On the other hand, HSR triggers thermotolerance, i.e. hyperthermia-treated cells show an impairment in their susceptibility to a subsequent heat-induced stress. This poses questions about efficacy and optimal strategy for anti-cancer therapy combined with hyperthermia treatment. To address these questions, we adapt our previous HSR model and propose its stochastic extension. We formalize the notion of a HSP-induced thermotolerance. Next, we estimate the intensity and the duration of the thermotolerance. Finally, we quantify the effect of a multimodal therapy based on hyperthermia and a cytotoxic effect of bortezomib, a clinically approved proteasome inhibitor. Consequently, we propose an optimal strategy for combining hyperthermia and proteasome inhibition modalities. In summary, by a mathematical analysis of HSR, we are able to support the common belief that the combination of cancer treatment strategies increases therapy efficacy.

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article.