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Our aim was to develop and validate clinical-pharmacogenetic prediction models of gemcitabine\/cisplatin or pemetrexed\/cisplatin treatment outcome and develop an algorithm for genotype-based treatment recommendations in malignant mesothelioma (MM). We genotyped 189\u2009MM patients for polymorphisms in gemcitabine, pemetrexed and cisplatin metabolism, transport and drug target genes and DNA repair pathways. To build respective clinical-pharmacogenetic models, pharmacogenetic scores were assigned by rounding regression coefficients. Gemcitabine\/cisplatin model was based on training group of 71 patients and included CRP, histological type, performance status, <jats:italic>RRM1<\/jats:italic> rs1042927, <jats:italic>ERCC2<\/jats:italic> rs13181, <jats:italic>ERCC1<\/jats:italic> rs3212986, and <jats:italic>XRCC1<\/jats:italic> rs25487. Patients with higher score had shorter progression-free (PFS) and overall survival (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). This model\u2019s sensitivity was 0.615 and specificity 0.812. In independent validation group of 66 patients the sensitivity and specificity were 0.667 and 0.641, respectively. Pemetrexed\/cisplatin model was based on 57 patients and included CRP, <jats:italic>MTHFD1<\/jats:italic> rs2236225, and <jats:italic>ABCC2<\/jats:italic> rs2273697. Patients with higher score had worse response and shorter PFS (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). This model\u2019s sensitivity was 0.750 and specificity 0.607. In independent validation group of 20 patients the sensitivity and specificity were 0.889 and 0.500, respectively. The proposed algorithm based on these models could enable the choice of the most effective chemotherapy for 85.5% of patients and lead to improved treatment outcome in MM.<\/jats:p>","DOI":"10.1038\/srep46537","type":"journal-article","created":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T11:41:05Z","timestamp":1492602065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Clinical-pharmacogenetic models for personalized cancer treatment: application to malignant mesothelioma"],"prefix":"10.1038","volume":"7","author":[{"given":"Katja","family":"Gori\u010dar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viljem","family":"Kova\u010d","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vita","family":"Dol\u017ean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,19]]},"reference":[{"key":"BFsrep46537_CR1","first-page":"160","volume":"2","author":"L Bonanno","year":"2013","unstructured":"Bonanno, L. 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