The NF-kB pathway plays a crucial role in immune response, cell inflammation, and cell death and survival, which is why it is such an important pathway to study in regards to ovarian cancer development and progression. Previous studies have shown the effects of this pathway and its relation to cancer stem-like cells that remain quiescent during remission and begin to proliferate again post chemotherapy and eventually reform tumors. This pathway is activated in one of two ways: the non-canonical or the canonical pathway, and it is pertinent to know which proteins in these pathways may be important to target when looking at relapse. One of the proteins of interest is Nuclear Factor κB-inducing Kinase (NIK), which I hypothesize is required to maintain ovarian cancer stem-like cells in the classical NF-kB pathway. I will assess NIK’s role in regards to chemoresistance and quiescence post chemotherapy by utilizing inducible CRISPR knockouts in the different ovarian cancer cell lines, OVCAR8, OVCAR4, OV90, and CaOV4 in order to knock out the NIK protein post-chemotherapy. I will then be able to look at the downstream effects of this knockout through both an in-vivo and in-vitro model to see if knocking out NIK proteins will result in less tumor growth post-relapse. I will do this through both a spheroid assay and through the use of a mouse model, which I expect will both show a less chemoresistant phenotype once NIK is knocked out.
