# Par-4 Regulation and Function in Breast Cancer Dormancy and Recurrence

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $61,196

## Abstract

Project Summary/Abstract
 Tumor progression – including resistance to therapy, metastasis, and recurrence – is
responsible for the majority of cancer deaths. Understanding how cancer cells survive treatment,
spread to distant sites, persist as dormant residual cells, and eventually recur is essential to improving
the treatment of this disease. Our long-term goal is to identify the pathways that regulate these
processes in order to prevent or treat tumor recurrence.
 To achieve this we are using conditional genetically engineered mouse (GEM) models of breast
cancer that allow for the mechanistic dissection of the processes of dormancy and recurrence. Using
these models, we have identified a functional role for the tumor suppressor par-4 in regulating survival
and recurrence of breast cancer cells after therapy. Par-4 is down-regulated in recurrent tumors from
three GEM models, and this down-regulation is both necessary and sufficient for tumor recurrence.
Similarly, in women with breast cancer, low par-4 expression is associated with a poor response to
neoadjuvant therapy and an increased risk of recurrence.
 However, nothing is known about the upstream pathways that regulate par-4 during dormancy
and recurrence. In addition, it is not known what downstream pathways par-4 regulates to inhibit
dormant cell survival and recurrence, or how par-4 affects metastasis. This proposal will address these
questions. In Aim 1, we will elucidate the pathways that regulate par-4 following oncogene inhibition
and in recurrent tumor cells, and determine how these contribute to dormant cell survival and
recurrence. In Aim 2, we will identify the molecular pathways regulated by par-4 expression, and
determine how these contribute to dormant cell survival and recurrence. In Aim 3, we will dissect the
temporal requirements for par-4 down-regulation during dormancy, recurrence, and metastasis. Our
work will provide insight into the regulation and function of par-4 during tumor recurrence and may
identify opportunities to develop therapies that target dormant cells and prevent tumor recurrence.

## Key facts

- **NIH application ID:** 10459140
- **Project number:** 7R01CA208042-06
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** James V Alvarez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $61,196
- **Award type:** 7
- **Project period:** 2021-08-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459140

## Citation

> US National Institutes of Health, RePORTER application 10459140, Par-4 Regulation and Function in Breast Cancer Dormancy and Recurrence (7R01CA208042-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10459140. Licensed CC0.

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