# Novel Biomarkers Predicting Blood Clots in Ovarian Cancer

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $419,571

## Abstract

Project Summary/Abstract
Venous thromboembolism (VTE) develops in about one-fourth of patients with ovarian cancer and is associated
with significant morbidity and mortality. Chemotherapy increases VTE risk, but administration of prophylactic
anticoagulation to all patients on chemotherapy is associated with a substantial risk of bleeding. Therefore, it is
crucial to identify patients with a higher risk of VTE. In the University of Texas MD Anderson Cancer Center
(MDACC) Ovarian Cancer Moon Shot program, we have assembled a cohort of 354 patients who have received
neoadjuvant chemotherapy. The availability of tumor specimens, blood samples, and an extensive clinical
database from these patients provides us a unique opportunity to investigate the novel predictive biomarkers for
VTE in ovarian cancer. Most previous studies on cancer thrombosis analyzed clinical, demographic, or
hemostatic factors already known to be risk factors for VTE in cancer patients instead of identifying tumor-specific
prothrombotic factors. We will explore cancer cell products that increase VTE risk and particularly investigate
the impact of cancer cell-derived podoplanin and mitochondria on VTE. We found mitochondria in plasma
samples of cancer patients and showed that ovarian cancer cells release mitochondria (both free and
microvesicle-embedded). Injection of mitochondria caused venous thrombi in mice, rich in neutrophils and
neutrophil extracellular trap (NETs). We speculate that mitochondria-targeted antioxidants and antibiotics
blocking the synthesis of chemotactic formylmethionine(fMet)-tagged peptides reduce cancer VTE. We found
that podoplanin is expressed on ovarian cancer cells and tumor-derived extracellular vesicles (EVs), and its
expression is increased by chemotherapy. Podoplanin-expressing EVs activate platelets, and their injection into
mice causes platelet-rich venous thrombi. We propose that a small molecule blocking podoplanin interaction with
platelets reduces cancer thrombosis. We will examine whether the number of mitochondria and concentration of
podoplanin in plasma predict VTE risk in ovarian cancer patients receiving chemotherapy. We will investigate
the effect of a mitochondria-targeted antioxidant, an antibiotic blocking synthesis of fMet peptides, and a
podoplanin inhibitor on venous thrombosis in a murine model of IVC ligation. Finally, we will compare the
mutation profile and mutation burden of mitochondria and nuclear genes in tumors of ovarian cancer patients
with and without VTE to identify the genetic changes in cancer cells associated with an increased VTE risk.

## Key facts

- **NIH application ID:** 10931748
- **Project number:** 5R01CA275762-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Vahid Afshar-Kharghan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $419,571
- **Award type:** 5
- **Project period:** 2023-09-19 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931748

## Citation

> US National Institutes of Health, RePORTER application 10931748, Novel Biomarkers Predicting Blood Clots in Ovarian Cancer (5R01CA275762-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10931748. Licensed CC0.

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