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Reprogramming Lipogenic Metabolism and Inflammation in High-risk Breast with Licochalcone A: A Novel Path to Cancer Prevention

  • Date: Monday, April 21, 2025
  • Time: 1:00pm EDT to 2:00pm EDT

Speaker

Atieh Hajirahimkhan, Ph.D.

Atieh Hajirahimkhan, Ph.D.
NCI NRSA Postdoctoral Fellow
Department of Surgery
Lurie Cancer Center Translational Bridge Fellow
Robert H. Lurie Comprehensive Cancer Center
Feinberg School of Medicine
Northwestern University

Dr. Atieh Hajirahimkhan is a medicinal chemist with extensive experience in natural products pharmacology and drug discovery. She completed her Ph.D. at the University of Illinois Chicago followed by an American Cancer Society postdoctoral fellowship (2018-2022), a current NCI-NRSA postdoctoral fellowship (2023-2025), and a Lurie Cancer Center Translational Bridge fellowship (2022-2024) in Dr. Seema Khan’s laboratory at Northwestern University. The presently available endocrine therapies used for breast cancer prevention have adverse side effects which has led to minimal acceptance and impact. Atieh's research interest is interventional breast cancer risk reduction through reversing oncogenic metabolism and inflammation in high-risk breast with minimal adverse effects. She is developing a promising candidate agent, L13, based on licochalcone A, with demonstrated efficacy against HR+ and HR- breast cancer subtypes, and a promising oral pharmacokinetics. Her career goal is to establish independent academic research in the medicinal prevention of cancer.

Abstract

Anti-estrogens have had limited impact on breast cancer (BC) prevention. Novel agents with better tolerability, and efficacy beyond estrogen receptor positive (ER+) BC, are needed. We are developing licochalcone A (LicA) as a BC prevention candidate.

We evaluated its antiproliferative effects in multiple breast cell lines and its suppression of ER+/- xenograft tumors in mice. Two independent cohorts of high-risk women breast tissues and ER+/- BC cell lines were treated with LicA followed by RNA sequencing, metabolism flux modeling, confirmatory transcriptomics and proteomics, and targeted and phenotypic approaches. We developed LicA’s oral formulations and conducted pharmacokinetic studies.

LicA suppressed proliferation and xenograft tumor growth. Mechanistically, it downregulates pivotal steps in PI3K-AKT-SREBP1-dependent lipogenesis and NF-kB-dependent inflammation. These changes lead to concerted reduction in inflammation, and lipids including membrane cholesterol and nucleotides essential for cell proliferation. Oral LicA’s promising pharmacokinetics warrants further studies to establish a novel non-endocrine drug for BC prevention.