Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Melanocortin-4 receptor antagonist TCMCB07 alleviates chemotherapy-induced anorexia and weight loss in rats
Xinxia Zhu, … , Aaron J. Grossberg, Daniel L. Marks
Xinxia Zhu, … , Aaron J. Grossberg, Daniel L. Marks
Published November 7, 2024
Citation Information: J Clin Invest. 2025;135(1):e181305. https://doi.org/10.1172/JCI181305.
View: Text | PDF
Research Article Oncology Article has an altmetric score of 76

Melanocortin-4 receptor antagonist TCMCB07 alleviates chemotherapy-induced anorexia and weight loss in rats

  • Text
  • PDF
Abstract

Cancer patients undergoing chemotherapy often experience anorexia and weight loss that substantially deteriorates overall health, reduces treatment tolerance and quality of life, and worsens oncologic outcomes. There are currently few effective therapeutic options to mitigate these side effects. The central melanocortin system, which plays a pivotal role in regulating appetite and energy homeostasis, presents a logical target for treating anorexia and weight loss. In this preclinical study, we evaluated the efficacy of TCMCB07, a synthetic antagonist of the melanocortin-4 receptor, in mitigating anorexia and weight loss in several rat models of chemotherapy: cisplatin, 5-fluorouracil, cyclophosphamide, vincristine, doxorubicin, and a combination of irinotecan and 5-fluorouracil. Our results indicate that peripheral administration of TCMCB07 improved appetite, stabilized body weight, preserved fat and heart mass, and slightly protected lean mass after multiple cycles of chemotherapy. Furthermore, combining TCMCB07 with a growth differentiation factor 15 antibody enhanced treatment effectiveness. Similar effects from TCMCB07 treatment were observed in a rat tumor model following combination chemotherapy. No notable adverse effects nor increased chemotherapy-related toxicities were observed with TCMCB07 treatment. These findings suggest that peripheral administration of TCMCB07 holds promise as a therapeutic approach for alleviating chemotherapy-induced anorexia and weight loss, potentially benefiting numerous patients undergoing chemotherapy.

Authors

Xinxia Zhu, Russell Potterfield, Kenneth A. Gruber, Emma Zhang, Samuel D. Newton, Mason A. Norgard, Peter R. Levasseur, Peng Bai, Xu Chen, Qingyang Gu, Aaron J. Grossberg, Daniel L. Marks

×
Options: View larger image (or click on image) Download as PowerPoint
TCMCB07 doses and serum concentrations in rats treated with cisplatin ch...

TCMCB07 doses and serum concentrations in rats treated with cisplatin chemotherapy


Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 9 news outlets
Posted by 22 X users
Referenced by 1 Bluesky users
4 readers on Mendeley
See more details