# Targeting the Opioidergic and Adrenergic Systems to Control Breast Cancers

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $310,000

## Abstract

Breast tumors vary in their molecular subtypes (luminal A, Luminal B, triple negative/basal-like and Her2 type).
Disparities in breast cancer persist in all types. The prevalence rates and prognosis of the four subtypes of
breast cancer appear to differ by race in the US. Recent studies have identified the immune response in the
tumor microenvironment of both HER2+ and basal tumors an important prognostic factor. We have recently
shown that intervention related to reduction of body stress via endorphin cell therapy into the brain suppresses
carcinogen-induced mammary tumor incidence, growth, malignancy rate, and metastasis in rat animal models
by increasing immune activities and altering inflammatory conditions in the tumor microenvironment. The
beneficial effect of endorphin cell therapy on cancer growth involves activation of the opioidergic system and
suppression of the adrenergic system in rats. We hypothesize that pharmacological agents targeting both the
opioidergic system and beta2-adrenergic system might offer an effective therapy for growth prevention of all
types of breast cancer cells. Furthermore, we hypothesize that simultaneous activation of delta-opioid
receptors and suppression of beta2-adrenergic receptors will be most effective. To test these hypotheses we
will employ established breast cancer cell lines and primary human tumor tissues that represent various breast
tumor subtypes in xenografts in athymic nude rats and humanized NSG mice. We will determine the efficacy
of a combined treatment of a delta-opioid receptor agonist and a beta2-adrenergic receptor antagonist in
reducing the growth and invasiveness in xenografts. We will determine effects of these agents on tumor cell
physiology by measuring various biochemical markers and signaling molecules of proliferation, apoptosis and
epithelial mesenchymal transition. We will study whether opioidergic and adrenergic agents alter immune cell
functions to affect tumor cell physiology. Furthermore, we will evaluate if the cross talk between opioidergic
and adrenergic agents is due to receptor dimerization on immune cells and/or breast tumor cells. We will
employ various cellular and molecular approaches, receptorology and gene knockdown techniques to
investigate molecular actions of opioidergic and beta2-adrenergic agents on breast cancer cell growth and
progression.
 Together these studies should show the effectiveness of combining an opioid agonist and beta2-adrenergic
antagonist for preventing growth of various types of breast cancer cells that may be easily translatable to clinic
for the treatment of patients with various subtypes of breast cancers.

## Key facts

- **NIH application ID:** 9930543
- **Project number:** 5R01CA208632-04
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** DIPAK KUMAR SARKAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $310,000
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930543

## Citation

> US National Institutes of Health, RePORTER application 9930543, Targeting the Opioidergic and Adrenergic Systems to Control Breast Cancers (5R01CA208632-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9930543. Licensed CC0.

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