# Alternative NF-kB activation in post-chemotherapy setting to elucidate novel mechanisms of ovarian cancer relapse

> **NIH NIH R01** · SAN DIEGO STATE UNIVERSITY · 2024 · $11,826

## Abstract

Project Summary
Ovarian cancer is the most lethal gynecological malignancy in the United States and although patients initially
respond to cytotoxic chemotherapy, most relapse with chemoresistant disease within 24 months. There are
several critical gaps in our knowledge of the mechanisms that support disease recurrence but research over the
last decade support the notion tumor-initiating cells (TICs), a subpopulation of drug resistant tumor cells, are
responsible for facilitating relapse and combination therapies targeting these elusive cells may lead to longer
remission or even cures. Although numerous genes and signaling pathways have been implicated in maintaining
TICs, there are several critical gaps in our understanding of the processes these cells use to survive cytotoxic
chemotherapy and successfully re-establish tumors. Our previous studies revealed an important role for
alternative NF-kB signaling in regulating stemness genes and supporting chemotherapy resistance. NF-kB is a
family of transcription factors that respond to signals in the TME to promote proliferation, chemoresistance, and
survival of cancer cells through activation of either RelA or RelB transcription factors. Clinical data from patients
undergoing neoadjuvant chemotherapy show that genes encoding alternative NF-kB family members are
significantly elevated in tumors resected following cytotoxic chemotherapy relative to pre-treatment levels.
Recent findings in our lab also implicate RelB in isolation and nutrient stress. These data lead us to our central
hypothesis that alternative NF-kB activation is critical for maintaining tumor-initiating cells that facilitate ovarian
cancer relapse. To investigate this hypothesis, the student will 1) Perform limiting dilution spheroid formation and
xenotransplantation studies using RelB or control knockout ovarian cancer cells and 2) investigate the
requirement for RelB signaling in metastasis ability in the presence and absence of chemotherapy. These
experiments will provide critical evidence not currently addressed in the parent grant or in prior published work
to distinguish the role of RelB in chemotherapy resistance versus tumor-initiating cell phenotypes. Given the
strong initial response to chemotherapy, it is of great interest to identify mechanisms that maintain TICs in ovarian
cancer. NF-kB regulates several gene programs that support stemness and survival pathways. Clarifying
whether this pathway imparts only chemotherapy resistance or whether it also supports long-term survival of
TICs and regeneration of heterogeneous tumors will improve our understanding of NF-kB in relapse and will
inform future therapeutic directions.

## Key facts

- **NIH application ID:** 11061618
- **Project number:** 3R01CA260281-02S1
- **Recipient organization:** SAN DIEGO STATE UNIVERSITY
- **Principal Investigator:** Carrie Danielle House
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $11,826
- **Award type:** 3
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11061618

## Citation

> US National Institutes of Health, RePORTER application 11061618, Alternative NF-kB activation in post-chemotherapy setting to elucidate novel mechanisms of ovarian cancer relapse (3R01CA260281-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11061618. Licensed CC0.

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