Christina Gewinner, PhD
- University College London Cancer Institute
- 2012 Skacel Family Scholar
Identification of novel drug targets for INPP4B-deficient ovarian tumours
Dr. Gewinner’s lab has previously identified a gene called inositol polyphosphate 4-phosphatase type II (INPP4B) which no longer functions in approximately 40% of ovarian tumors. Patients with such tumors have poor survival rates. She has demonstrated that INPP4B deficiency is similar to BRCA1/2 mutations in that DNA repair is defective in cells which harbor these deficiencies. Recently in clinical trials, inhibitors that target DNA repair enzymes have been used to treat ovarian cancer patients with BRCA1/2 mutations. These inhibitors are effective at forcing tumor cells to undergo cell death. Because of the similarity of INPP4B deficiency to BRCA1/2, Dr. Gewinner hypothesizes that INPP4B-deficient ovarian tumors may also respond to inhibitor treatment and that INPP4B can be used as a predictive diagnostic biomarker.
Brigitte Thériault, PhD
- Ontario Cancer Institute
Modulation of KIF14 overexpression in ovarian cancer
Dr. Thériault’s lab had previously discovered that the gene KIF14 is present in high amounts in the majority of ovarian cancers, and that patients with high KIF14 have much worse survival than patients with low KIF14. KIF14 is normally found in cells that are growing and dividing and is usually not found in adult human tissues. Her prior research in cell cultures and in animal models has shown that accumulation of KIF14 leads to tumor spread and blocking KIF14 causes tumor cell death. Dr. Thériault’s goal in this project is to understand how tumors accumulate such high amounts of KIF14 so that she can find ways to block KIF14 production, stop tumor cell growth, and improve the survival of ovarian cancer patients.
Anne Noonan, MB BCh BAO, MSc, MRCPI
- National Cancer Institute
- 2012 Gilman Family Scholar
Proteomic biomarker development for optimal sequencing of doxetaxel & SMACmimetic
The drug TL32711 can stimulate ovarian cancer cell death by decreasing proteins that inhibit cell death and decreasing signaling through the NFkB signalling pathway that is known to be overactive in ovarian cancer. This cascade of protein changes could work with a traditional chemotherapy agent called docetaxel to increase ovarian cancer cell death. Dr. Noonan will focus on an enzyme called caspase-8 which is an important link between NFkB and cell death pathways to see if she can tip the balance toward cell death in ovarian cancer tumors. The aim of Dr. Noonan’s project is to determine how best to combine TL32711 and docetaxel and to discover if protein biomarkers can aid the selection of patients for this drug combination in future clinical trials.