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Principal Investigator: ANDREW K. GODWIN
Organization: UNIVERSITY OF KANSAS MEDICAL CENTER
Fiscal Year: 2024
Award: $298,484
Funding agency: National Cancer Institute
PROJECT SUMMARY
Ovarian cancer is a silent killer that strikes with few, if any, symptoms. By the time a woman knows she has it,
the cancer is often advanced and the outlook grim. However, if epithelial ovarian cancer is caught early the
prognosis for the patient is excellent. Developing non-invasive and highly specific blood-based tests for pre-
symptomatic screening and early detection of ovarian cancer is therefore crucial. This is especially essential
since obtaining a biopsy is difficult, costly, and sometimes not even an option. In addition, most blood biomarkers
to date lack the necessary sensitivity and specificity for early detection of this silent killer. A fundamental
challenge is the extremely low concentrations of circulating biomolecules released from the developing tumors
at pre-clinical stages which can be 10,000-fold lower than their clinically detectable levels. Therefore, there is a
pressing need to uncover novel biomarkers, apply new strategies, and develop robust technologies to propel the
advancement of cancer diagnostics, especially in a disease such as ovarian cancer. We have focused our efforts
on small extracellular vesicles (sEVs), primarily small and large exosomes derived from the endolysosomal
pathway, which play important roles in cellular communication, immune response, and cancer progression via
transfer of a selective repertoire of biomolecules. sEVs/exosome release is significantly increased in most
neoplastic cells, including ovarian cancer and occurs continuously at all stages of tumor development. Tumor-
derived sEVs accumulate in human blood and malignant effusions. These vesicles carry enriched subsets of
biomolecules mirroring the tumor cells of origin, such as signaling proteins, tumor antigens, and functional RNAs
(mRNA and miRNAs), which offer a new strategy to surmount the challenge in reliable detection of intrinsically
low-level serum markers during early malignant transformation. Thus, the constitutive release and enrichment
of certain tumor markers within sEVs present distinctive opportunities for early cancer diagnosis. We
hypothesize that circulating sEVs, much akin to circulating tumor cells but more robust due to their active release
and incredible stability in bodily fluids, represent a greater source for the discovery of exo-biomarkers for early
detection, potentially while still confined to the fallopian tube. In addition, sEVs can serve as a 'liquid biopsy’ to
assess benefits and treatment responses in real time in cancer patients. Our innovative application merges EV
biology with nano-material/microfluidic technology to develop an advanced microfluidic platform to capture and
detect ovarian cancer-derived sEVs with high specificity and sensitivity from the circulation. This approach will
integrate validated fallopian tube and ovarian cancer associated exo-protein biomarkers (SA1), which will be
applied to a second-generation nano-engineered EV analysis chip (SA2). These studies will be followed by
clinical validation using longitudinal samples collected from asymptomatic women who later develop epithelial
ovarian cancer (SA3). Our ultimate goal is to develop a reliable blood-based assay that, when used in
conjunction with current screening approaches will decrease the mortality from ovarian cancer.
Terms: <3-D><3-Dimensional><3D><Abscission><Advanced Cancer><Advanced Malignant Neoplasm><Advisory Committees><Area><Assay><BRCA 1/2 mutations><BRCA mutations><BRCA1/2 mutations><BRCA1/2mut><BRCAmut><Benign><Bioassay><Biological Assay><Biological Markers><Biology><Biopsy><Blood><Blood Plasma><Blood Reticuloendothelial System><Blood Sample><Blood capillaries><Blood specimen><Body Fluids><Body Tissues><Breast Cancer><CA-125><CA-125 Antigen><CA125><Cancer Antigen 125><Cancer Control><Cancer Control Science><Cancer Detection><Cancer Diagnostics><Cancer Patient><Cancer cell line><Cancers><Carbohydrate Antigen 125><Carcinoma in Situ><Cell Line><CellLine><Cervical Cancer><Cervix Cancer><Circulation><Clinical><Clinical Sensitivity><Colon Cancer><Colon Carcinoma><Communication><Companions><Death Rate><Detection><Development><Diagnosis><Diagnostic Sensitivity><Disease><Disorder><Drops><Early Diagnosis><Echography><Echotomography><Engineering><Epithelial ovarian cancer><Excision><Extirpation><Fallopian Tubes><Fingerprint><Functional RNA><General Population><General Public><Generations><Goals><Human><Immune Precipitation><Immune response><Immunoassay><Immunological response><Immunoprecipitation><Intervention><Intervention Strategies><Intraepithelial Carcinoma><Malignant><Malignant - descriptor><Malignant Breast Neoplasm><Malignant Cervical Neoplasm><Malignant Cervical Tumor><Malignant Neoplasm of the Cervix><Malignant Neoplasms><Malignant Ovarian Neoplasm><Malignant Ovarian Tumor><Malignant Tumor><Malignant Tumor of the Cervix><Malignant Tumor of the Cervix Uteri><Malignant Tumor of the Ovary><Malignant Uterine Cervix Neoplasm><Malignant Uterine Cervix Tumor><Malignant neoplasm of cervix uteri><Malignant neoplasm of ovary><Mammalian Oviducts><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Medical Ultrasound><Messenger RNA><Methods><Micro RNA><MicroRNAs><Microfluidics><Modern Man><Nanochip Analytical Device><Neoplasm Circulating Cells><Non-Coding><Non-Coding RNA><Non-translated RNA><Noncoding RNA><Nontranslated RNA><Operative Procedures><Operative Surgical Procedures><Outcome><Ovarian><Ovary><Ovary Cancer><Pathway interactions><Patients><Pattern><Plasma><Plasma Serum><Play><Population Control><Preinvasive Carcinoma><Printing><Proteins><Proteomics><Public Health><Removal><Reporting><Reproducibility><Research Specimen><Reticuloendothelial System, Serum, Plasma><Risk><Role><Salpinx><Sampling><Screening for Ovarian Cancer><Screening for cancer><Sensitivity and Specificity><Serous><Serum Markers><Signaling Factor Proto-Oncogene><Signaling Pathway Gene><Signaling Protein><Solid Neoplasm><Solid Tumor><Source><Specificity><Specimen><Strains Cell Lines><Surgical><Surgical Interventions><Surgical Procedure><Surgical Removal><Symptoms><T-Stage><TM-MKR><Task Forces><Technology><Testing><Time><Tissues><Training><Tumor Antigens><Tumor Cell><Tumor Markers><Tumor stage><Tumor-Associated Antigen><Tumor-Derived><Ultrasonic Imaging><Ultrasonogram><Ultrasonography><Ultrasound Diagnosis><Ultrasound Medical Imaging><Ultrasound Test><Untranslated RNA><Uterine Cervix Cancer><Uterine Tubes><Vagina><Validation><Vesicle><Woman><advisory team><annual screening><bio-markers><biologic marker><biomarker><biomarker array><biomarker panel><cancer antigens><cancer diagnosis><cancer in the colon><cancer progression><candidate biomarker><candidate marker><candidate validation><capillary><circulating neoplastic cell><circulating tumor cell><clinical diagnosis><clinical translation><clinically translatable><computer chip><cost><cultured cell line><curative intervention><curative therapeutic><curative therapy><curative treatments><detection assay><developmental><diagnostic platform><diagnostic system><diagnostic ultrasound><disease risk><disorder risk><early biomarkers><early cancer detection><early detection><early detection biomarkers><early detection markers><effusion><exosome><extracellular vesicles><high risk group><high risk individual><high risk people><high risk population><host response><image-based method><imaging method><imaging modality><immune system response><immunoresponse><in situ cancer><innovate><innovation><innovative><interventional strategy><liquid biopsy><mRNA><malignancy><malignant breast tumor><marker panel><miRNA><miRNAs><microchip><microfluidic technology><microsystems><mortality><mortality rate><mortality ratio><mutation carrier><nano><nano chip><nano chip Analytical Device><nano engineering><nano pattern><nanochip><nanoengineering><nanomaterials><nanopattern><neoplasm progression><neoplasm/cancer><neoplastic cell><neoplastic progression><new marker><noncoding><novel><novel biomarker><novel marker><ovarian cancer><ovarian cancer detection><ovarian cancer early detection><ovarian cancer early screening><oviduct><pathway><patient prognosis><pre-clinical><pre-symptomatic testing><preclinical><presymptomatic testing><prevention service><protein biomarkers><protein markers><protein profiling><resection><response to therapy><response to treatment><routine screening><screening><screening cancer patients><screenings><self assembly><social role><sonogram><sonography><sound measurement><surgery><therapeutic response><therapy response><three dimensional><tool><treatment response><treatment responsiveness><tumor><tumor biomarker><tumor progression><tumor specific biomarker><tumor-specific antigen><ultrasound imaging><ultrasound scanning><validations><µfluidic><µfluidic technology>