Funded Research: 2016
Alexandra Snyder, MD
Gynecologic Medical Oncology and Immunotherapeutics Service
Memorial Sloan Kettering Cancer Center
Dr. Snyder is a translational physician-scientist at Memorial Sloan Kettering Cancer Center (MSKCC) who specializes in the study of tumor genetics and response to checkpoint blockade immunotherapy in solid tumors, with a particular focus on ovarian cancer.
The Genomic and Immune Landscape Following Neoadjuvant Chemotherapy in Ovarian Cancer
Immunotherapy with T-cell checkpoint inhibition can improve long-term disease control for patients with diverse malignancies including ovarian cancer. By increasing the mutational burden and activating the immune system, chemotherapy may increase responsiveness to immune therapies in ovarian cancers as well as other types of solid tumors. Using a variety of sequencing and immunologic techniques, we will evaluate genomic and inflammatory changes that occur after the administration of cytotoxic chemotherapy. We hypothesize that neoadjuvant cytotoxic chemotherapy will lead to a more “inflamed” tumor phenotype with increased mutational burden, neoantigen expression, and immune infiltration in patients with ovarian cancer. This study will help us to understand the immunologic effects of cytotoxic chemotherapy, which may prime the tumor microenvironment for further immunotherapy. This study may inspire clinical trials of combination or sequential therapies for ovarian cancer which manipulate the tumor mutational and immune landscapes into more immunogenic phenotypes, thus overcoming the current limitations to immunotherapy.
2016 Grant Recipient for Continued Funding
George Preti, Ph.D.
Monell Chemical Senses Center
A Novel Multidisciplinary Approach to Development of an Effective Ovarian Cancer Screening Diagnostic using Volatile Biomarkers
Recent literature suggests that volatile organic compounds (VOC) or odorants are altered in the earliest stages of cancer even before cancer can be detected with currently available imaging devices. These odorants remain a relatively untapped source for cancer detection information. Research has shown that minute quantities of odorants can be detected using trained detection dogs and electronic devices, as well as identified using analytical analyses providing a sensitive target for early cancer detection. We propose a new method of screening for ovarian cancer using analysis of odorants which has great potential in decreasing future cancer deaths.
We hypothesize that the odorants emanating from ovarian tissue will change with the onset of cancer-related metabolism and will provide a reliable, detectable substrate for early detection, allowing more effective treatment. Our hypothesis is further supported by recent studies that suggest that canine olfaction can (a) distinguish normal ovarian epithelial tissue from ovarian epithelial carcinoma (b) distinguish blood samples from healthy women from those women with ovarian cancer and (c) demonstrate that ovarian epithelial carcinoma has a different, distinguishable odor profile from other cancers of the reproductive tract.
Early successes have also been achieved using electronic sensors (artificial noses) to distinguish the volatile organic compounds in cancer patients from controls. To detect this distinctive odorant signature, the proposed collaborative research will employ a multimodal approach including canine olfaction, as well as other analytical tools. Pilot research will evaluate and compare the ability of canine and other sensors to detect the total odorant signatures of serum samples in ovarian cancer versus controls. We also aim to identify the odorants that distinguish disease from healthy samples.
We hypothesize that the study of disease-detecting olfaction in dogs can facilitate the development of nanotechnology-based olfactory sensors (e-noses). Data from our proposed study will allow us to begin the translation of these findings to the development of a device that can reliably detect ovarian cancer at an early, treatable stage in the doctor’s office.
2016 Grant Recipient for Continued Funding
Dr. Cynthia Otto
DVM, PhD, DACVECC, DACVSMR, CCRT –
Executive Director, Penn Vet Working Dog Center
University of Pennsylvania
School of Veterinary Medicine
Foster, dog sponsored by KOH for research in detecting ovarian cancer in blood