The overall goal of the MD Anderson Cancer Center SPORE in Ovarian Cancer is to test and translate novel therapeutic strategies, including those to overcome adaptive resistance to conventional cytotoxic chemotherapy, poly (ADP-ribose) polymerase inhibitors (PARPi), anti-angiogenic agents (bevacizumab) and immune checkpoint blockade. We have successfully implemented measures to increase recruitment of women and underrepresented minorities to our Developmental Research Program (DRP) and Career Enhancement Program (CEP). Over the last 22 years, our SPORE investigators have been highly productive with major discoveries. These include: 1) conducted the SPORE and EDRN-supported Normal Risk Ovarian Screening Study (NROSS) where 71% of cases were detected in stage I or II; 2) identified biomarkers that detect 18% of CA125 negative cases; 3) developed a 4-biomarker algorithm that detects advanced stage disease earlier than the CA125-based NROSS algorithm; 4) found anti-TP53 autoantibodies elevated 8 months before CA125 and 22 months before diagnosis; 5) observed a 54% objective response rate to anti-angiogenic therapy with aflibercept and docetaxel; 6) completed a trial targeting Dll4; 7) demonstrated that CSF1R inhibitors can deplete macrophages and reduce resistance to anti-VEGF therapy; 8) demonstrated significant activity of selumetinib in low-grade ovarian cancers and completed an international phase III trial of another potent MEK inhibitor trametinib; and 9) developed a robust biomarker panel that predicts response to PARPi and completion of multiple trials combining PARPi with rationally selected drugs in high-grade ovarian cancer.
What is a SPORE?
SPORE stands for Specialized Program of Research Excellence. Funded by the National Cancer Institute (NCI), the program is part of a nationwide initiative designed to speed the flow of promising knowledge from the laboratory to the clinic, where it can help patients the most, as well as from the clinic back to the laboratory. The ultimate goal of this NCI initiative is to reduce cancer incidence and mortality of cancers at differing sites or that share a common cause and to improve the quality of life for cancer patients.
SPORE funding is awarded to institutions with expertise in cancer research and a track record of turning promising laboratory findings into advances in patient care. The MD Anderson Cancer Center SPORE in Ovarian Cancer consists of 4 projects: Project 1 and Project 4 investigators tackle therapeutic resistance to PARP inhibitors and immune checkpoint blockers from multiple directions to speed progress and improve outcomes for women with ovarian cancer. Both projects have the potential to enhance T-cell infiltration in tumors and impart immunologic memory, which is particularly important given the likelihood of this cancer to recur. In Project 2, we will develop a novel TROP2-targeted CAR-NK therapy. In Project 3, we will develop therapy aimed at the tumor microenvironment using a novel EGFL6 targeted monoclonal antibody. The Ovarian Cancer SPORE also includes a Career Enhancement Program (CEP) and Developmental Research Program (DRP). The CEP trains physician-scientists, clinical investigators, and laboratory-based investigators to formulate research plans with clinically testable hypotheses. The SPORE CEP provides awardees with an opportunity to learn through their experience in conducting a research project with the advice from a clinical mentor, a laboratory mentor, and members of their own mentoring team. We encourage minority and women faculty members from participating institutions to apply for a CEP award. The purpose of the DRP is to fund promising projects by investigators whose current work may not focus exclusively on ovarian cancer, but who propose highly innovative translational studies of ovarian cancer that could become full SPORE projects or compete for funding outside of the SPORE. The DRP allows us to recruit investigators into the ovarian cancer research community.
Overall, our translational studies are conducted in an optimal environment with a team directed towards improving clinical outcomes of women with ovarian cancer.