# Targeting uterine serous carcinoma with antibody-drug conjugates

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $204,372

## Abstract

PROJECT SUMMARY/ABSTRACT
This application is being submitted in response to the Notice of Special Interest (NOSI) identified as “NOT-CA-
24-044.” In recent years, antibody-drug conjugates (ADCs) such as the HER2 ADC trastuzumab deruxtecan (T-
DXd) have emerged as a powerful therapeutic strategy across solid tumors, with dozens of new ADCs in
development. Thus, we have strong interest in developing ADCs as a therapeutic strategy for uterine serous
carcinoma (USC), in line with our long-term goal to optimize biomarker-driven therapy in gynecologic diseases.
To this end, we propose two specific aims: Aim 1. To determine the expression pattern of emerging ADC targets,
using a tissue microarray of 100 endometrial cancers containing at least 50 USCs. We will perform
immunostaining for emerging ADC targets using well-established assays, several of which are already deployed
in the CLIA environment. We hypothesize that many ADC targets are expressed in USC, and better
understanding of the relative expression pattern in USC may seed better therapeutic trials. Aim 2. To determine
the antitumor activity of T-DXd or datopotamab deruxtecan (Dato-DXd), alone and in combination with the WEE1
inhibitor azenosertib in vitro and in vivo, using well-characterized models of USC. We hypothesize that USC will
be sensitive to many ADCs such as T-DXd and Dato-DXd, and that azenosertib may enhance their efficacy,
based on preliminary work that WEE1 inhibition can enhance activity of T-DXd. Of note, the WEE1 inhibitors
adovasertib and azenosertib have shown intriguing activity in USC, with molecular alterations such as TP53
mutation status thought to contribute to increase sensitivity. Taken together, we will demonstrate the frequency
of expression of different ADC targets and their overlap in USC. We will also test whether we can enhance the
activity of T-DXd and Dato-DXd with WEE1 inhibitor combinations. If so, this work will provide preliminary data
not only for planning of clinical trials with T-DXd and azenosertib, but will also allow us to pursue the same
combination strategy using other ADCs with topoisomerase payloads.

## Key facts

- **NIH application ID:** 11124339
- **Project number:** 3P50CA281701-02S2
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** ROBERT C BAST
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $204,372
- **Award type:** 3
- **Project period:** 2023-09-19 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11124339

## Citation

> US National Institutes of Health, RePORTER application 11124339, Targeting uterine serous carcinoma with antibody-drug conjugates (3P50CA281701-02S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11124339. Licensed CC0.

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