2. Academic Validation
  3. Single Dose of a Small Molecule Leads to Complete Regressions of Large Breast Tumors in Mice

Single Dose of a Small Molecule Leads to Complete Regressions of Large Breast Tumors in Mice

  • ACS Cent Sci. 2025 Jan 22;11(2):228-238. doi: 10.1021/acscentsci.4c01628.
Michael P Mulligan 1 2,  Matthew W Boudreau 1 2,  Brooke A Bouwens 2 3,  Yoongyeong Lee 4,  Hunter W Carrell 1 2,  Junyao Zhu 3,  Spyro Mousses 5,  David J Shapiro 3 6,  Erik R Nelson 2 6 7 8 9,  Timothy M Fan 2 6 10,  Paul J Hergenrother 1 2 6
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
  • 2 Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
  • 3 Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
  • 4 Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, United States.
  • 5 Systems Oncology, Scottsdale, Arizona 85255, United States.
  • 6 Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
  • 7 Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
  • 8 Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
  • 9 Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
  • 10 Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, United States.
PMID: 40028352 DOI: 10.1021/acscentsci.4c01628
Abstract

Patients with Estrogen Receptor α positive (ERα+) breast Cancer typically undergo surgical resection, followed by 5-10 years of treatment with Adjuvant endocrine therapy. This prolonged intervention is associated with a host of undesired side effects that reduce patient compliance, and ultimately therapeutic resistance and disease relapse/progression are common. An ideal Anticancer therapy would be effective against recurrent and refractory disease with minimal dosing; however, there is little precedent for marked tumor regression with a single dose of a small molecule therapeutic. Herein we report ErSO-TFPy as a small molecule that induces quantitative or near-quantitative regression of tumors in multiple mouse models of breast Cancer with a single dose. Importantly, this effect is robust and independent of tumor size with eradication of even very large tumors (500-1500 mm3) observed. Mechanistically, these tumor regressions are a consequence of rapid induction of necrotic cell death in the tumor and are immune cell independent. If successfully translated to human Cancer patients, the benefits of such an Anticancer drug that is effective with a single dose would be significant.

Figures
Products