Anti-Cancer Drug Resistance Causal Modeling from Lentiviral-Vector Integration Site Studies

Evolution plays a key role in cancer as the result of the accumulation of geneticalterations which provide selective advantages to a tumor cell allowing resistance toanti-cancer drugs. Unfortunately however the identification of the driver mutationsand thus the mechanisms underlying anti-cancer drug resistance (ACDR) still remainsa challenge. We previously demonstrated that lentiviral vectors (LVs) when properlymodified might integrate near specific genes alter their expression and induce canceror ACDR in vivo and in vitro. The analysis of vector-cellular genomic junctionsin tumor or ACDR cells allowed identifying causative genes of HER2+ breast cancercell line using a statistical approach defined Common Insertion Sites (CISs) thathighlight genomic regions targeted at significantly higher frequency than expected bya random distribution. The reconstruction of cumulative cancer progressionfrom 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 andco-occurring genes using cumulative cancer progression from cell line CIS genes andinvestigating the relation between them.