Abstract 2692: Overexpression of serine hydroxy methyl transferase 2 (SHMT2) in high grade prostate cancers as a marker of tumor response to oxaliplatin

Prostate cancer is one of the leading causes of death from cancer in men and its incidence is constantly rising. In most cases, the prognosis of patients is defined according to staging, PSA levels and Gleason score, which differentiates low grade (Gleason < 4) and high grade (Gleason ≥ 4) cancers. High-grade tumors are associated with high metastatic potential and poor prognosis. They are currently treated with hormone therapy, to which docetaxel is added when they become resistant to the anti-androgen. However, response rates remain very low. Clinical trials with other chemotherapeutic agents such as mitoxantrone, vinorelbine or oxaliplatin have been performed, yet with limited success. It was reported that an expression signature of 86 genes could distinguish low-grade and high-grade tumors, with a reliability of 81% (True et al. PNAS 2006 103:10991-6). We used an in silico approach to explore the NCI databases, which allow access to both gene expression profiles of 60 human tumor cell lines and their in vitro sensitivity to thousands of anticancer drugs. After extraction of the expression profiles of the 86 genes of the True's signature, we calculated, for each gene, the Pearson coefficients of correlation (r) between their expression level in the 60 cell lines and cell sensitivity to 140 core anticancer compounds, expressed as the antilog of IC50. A positive r-value is associated to drug efficacy, whereas a negative r-value is associated to drug resistance. Among the 86 genes, the expression of 45 genes was correlated with the sensitivity to various compounds with an r-value +0.3 (p