Dr. Springett’s research has focused on validation and targeting of LPAAT-beta (lysophosphatidic acid acyltransferase; a phosphatidic acid generating enzyme that regulates cell growth and proliferation) in ovarian and pancreatic cancer. Accomplishments of Dr. Springett and colleagues in this area include: 1) demonstration that LPAAT-beta is over expressed in ovarian and endometrial cancers; 2) discovery that LPAAT-beta is a prognostic marker and that expression correlates with poor clinical outcome in ovarian cancer; 3) discovery that LPAAT-beta is expressed in pancreatic cancer; and 4) demonstration that small molecule inhibitors of LPAAT-beta have therapeutic potential in animal models of ovarian cancer. They are working to identify new LPAAT-beta inhibitor pharmacophores that are suitable for translation to phase I trials.
Their work also focuses on developing and implementing biomarker-driven therapeutics into patient-based therapeutic trials. They conducted a phase I dose-escalation study of MK-2461 (a selective inhibitor of c-Met, an oncogene that contributes to malignant transformation and tumor cell metastasis in patients with advanced cancer). The biomarker-driven trial enrolled patients with evidence of c-Met activation in their tumor specimens to test safety, tolerability and preliminary efficacy.