title: Engineered reversal of drug resistance in cancer cells--metastases suppressor factors as change agents.
abstract: Building molecular correlates of drug resistance in cancer and exploiting them for therapeutic intervention remains a pressing clinical need. To identify factors that impact drug resistance herein we built a model that couples inherent cell-based response toward drugs with transcriptomes of resistant/sensitive cells. To test this model, we focused on a group of genes called metastasis suppressor genes (MSGs) that influence aggressiveness and metastatic potential of cancers. Interestingly, modeling of 84 000 drug response transcriptome combinations predicted multiple MSGs to be associated with resistance of different cell types and drugs. As a case study, on inducing MSG levels in a drug resistant breast cancer line resistance to anticancer drugs caerulomycin, camptothecin and topotecan decreased by more than 50-60%, in both culture conditions and also in tumors generated in mice, in contrast to control un-induced cells. To our knowledge, this is the first demonstration of engineered reversal of drug resistance in cancer cells based on a model that exploits inherent cellular response profiles.
authors.affiliation: G.N.R. Knowledge Centre for Genome Informatics, Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi 110 007, India, Biomaterials Group, Indian Institute of Chemical Technology, Hyderabad 500 607, India and Animal House, Centre For Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Vinod Kumar
authors.initials: VK
authors.lastname: Yadav
authors.forename: Akinchan
authors.initials: A
authors.lastname: Kumar
authors.forename: Anita
authors.initials: A
authors.lastname: Mann
authors.forename: Suruchi
authors.initials: S
authors.lastname: Aggarwal
authors.forename: Maneesh
authors.initials: M
authors.lastname: Kumar
authors.forename: Sumitabho Deb
authors.initials: SD
authors.lastname: Roy
authors.forename: Subrata Kumar
authors.initials: SK
authors.lastname: Pore
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Banerjee
authors.forename: Jerald
authors.initials: J
authors.lastname: Mahesh Kumar
authors.forename: Ram Krishna
authors.initials: RK
authors.lastname: Thakur
authors.forename: Shantanu
authors.initials: S
authors.lastname: Chowdhury
mesh_terms: D060846:Cell Engineering; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism