@article {ZANDER1821, author = {THILO ZANDER and JIA XUE and GABRIEL MARKSON and FELIX DAHM and CHRISTOPH RENNER}, title = {Satraplatin Demonstrates High Cytotoxic Activity Against Genetically Defined Lymphoid Malignancies}, volume = {42}, number = {4}, pages = {1821--1832}, year = {2022}, doi = {10.21873/anticanres.15658}, publisher = {International Institute of Anticancer Research}, abstract = {Background/Aim: Satraplatin is an oral platinum analog with proven clinical efficacy and a more favorable toxicity profile, although with increased hematotoxicity, when compared to cisplatin. Hence, we carried out a systematic biomarker analysis to identify hematological malignancies with high susceptibility to satraplatin. Materials and Methods: Half-maximal inhibitory concentrations (IC50) for satraplatin and cisplatin were determined for 66 different cancer cell lines by CTG Luminescent Cell Viability Assay. In a second step, whole transcriptome RNA sequencing and whole-exome DNA sequencing technology followed by unbiased analysis of gene expression, gene mutation and copy number levels were performed and correlated with drug efficacy. Results: Satraplatin was significantly more active against hematological malignancies compared to solid organ cancer. In addition, satraplatin showed a significantly more potent antiproliferative activity compared to cisplatin in most lymphoma cell lines achieving sub micromolar IC50 values. Single BCL2 apoptosis regulator (BCL2) gene mutation and 9p21 copy-number deletions including S-methyl-5{\textquoteright}-thioadenosine phosphorylase (MTAP) deficiency were identified as key characteristics for high sensitivity to satraplatin. Conclusion: Satraplatin demonstrated a high cytotoxic activity in genetically well-defined hematological malignancies which is distinct from that of cisplatin. MTAP deficiency was identified as biomarker of enhanced satraplatin efficacy in hematological cancer-derived cell lines. These data in combination with the lipophilicity of satraplatin provide the rationale for targeting specific lymphatic entities such as primary central nervous system lymphoma and cutaneous T-cell lymphoma to improve clinical outcome.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/42/4/1821}, eprint = {https://ar.iiarjournals.org/content/42/4/1821.full.pdf}, journal = {Anticancer Research} }