Exploiting the conditional vulnerabilities caused by TTFields exposure

Dr. Story hypothesizes that aside from disrupting mitosis, TTFields downregulate DNA repair pathways and initiate DNA replication stress, resulting in DNA damage, the generation of R-loops, collapsed replication forks, and eventual mitotic catastrophe. Agents that interfere with replication fork maintenance or DNA repair may be more lethal when combined with TTFields. Thus, he sets out to test combinatorial therapies involving agents that target or enhance replication stress, TTFields and radiation, in in vitro and ex vivo models of lung and pancreatic cancers.