Anti-Cancer Drug Resistance Causal Modeling from Lentiviral-Vector Integration Site Studies
$ 64.5
Description
Evolution plays a key role in cancer as the result of the accumulation of genetic alterations, which provide selective advantages to a tumor cell, allowing resistance to anti-cancer drugs. Unfortunately, however, the identification of the driver mutations and thus the mechanisms underlying anti-cancer drug resistance (ACDR) still remains a challenge. We previously demonstrated that lentiviral vectors (LVs), when properly modified, might integrate near specific genes, alter their expression and induce cancer or ACDR in vivo and in vitro. The analysis of vector-cellular genomic junctions in tumor or ACDR cells allowed identifying causative genes of HER2+ breast cancer cell line using a statistical approach defined Common Insertion Sites (CISs) that highlight genomic regions targeted at significantly higher frequency than expected by a random distribution. The reconstruction of cumulative cancer progression from CIS genes has not been yet addressed and may produce causative gene networks. The aim of this project is studying anti-cancer drug resistance from exclusive and co-occurring genes using cumulative cancer progression from cell line CIS genes and investigating the relation between them.