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Updated: Jul 24, 2025

The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
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Development of a peptide drug restoring AMPK and adipose tissue functionality in cancer cachexia

Honglei Ji1, Felix Englmaier2, Pauline Morigny1

  • 1Institute for Diabetes and Cancer, Helmholtz Diabetes Center, Helmholtz Center Munich, 85764 Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Unit, Heidelberg University Hospital, 69120 Heidelberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|July 6, 2023
PubMed

Insights

Researchers developed Pen-X-ACIP, a novel peptide therapy that stabilizes AMP-activated protein kinase (AMPK) in adipose tissue, effectively combating cancer cachexia by inhibiting lipolysis and preserving body mass.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Cancer cachexia is a debilitating condition impacting cancer patient survival and quality of life.
  • Adipose tissue dysfunction, driven by AMP-activated protein kinase (AMPK) complex destabilization, is a key factor in cancer cachexia.
  • Current treatments for cancer cachexia remain a significant unmet clinical need.

Purpose of the Study:

  • To develop and optimize a novel peptide therapeutic for cancer cachexia.
  • To investigate the efficacy of Pen-X-ACIP in preventing cachexia-related adipose tissue dysfunction.
  • To establish proof of concept for a new therapeutic strategy against cancer cachexia.

Main Methods:

  • Development of Pen-X-ACIP, a peptide fusing an AMPK-stabilizing moiety (ACIP) with a cell-penetrating peptide (penetratin) via click chemistry.
  • In vitro assessment of Pen-X-ACIP uptake by adipocytes, lipolysis inhibition, and AMPK signaling restoration.
  • In vivo studies involving systemic delivery of Pen-X-ACIP in tumor-bearing animals to evaluate its effects on cachexia progression, tumor growth, and tissue mass.

Main Results:

  • Pen-X-ACIP demonstrated efficient uptake by adipocytes, inhibited lipolysis, and restored AMPK signaling.
  • Intraperitoneal injection of Pen-X-ACIP led to favorable adipose tissue uptake.
  • Systemic administration of Pen-X-ACIP in tumor-bearing animals prevented cancer cachexia progression, preserved body weight and adipose tissue mass, without impacting tumor growth or causing side effects in other organs.
  • Pen-X-ACIP showed anti-lipolytic activity in human adipocytes.

Conclusions:

  • Pen-X-ACIP is a promising therapeutic candidate for cancer cachexia, demonstrating efficacy in preclinical models.
  • The peptide effectively targets adipose tissue dysfunction by stabilizing AMPK signaling.
  • Pen-X-ACIP offers a potential first-in-class therapeutic platform for clinical development against cancer cachexia.
Keywords:
AMPKadipose tissuecachexiacancermetabolic dysfunctionpeptide-drug

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