TWEAK–Fn14 and ER stress in cancer- and age-related muscle loss

TWEAK/Fn14/UPR Signaling in Skeletal Muscle Wasting

NIH-funded research University of Houston · NIH-11260265

This work will explore whether blocking the TWEAK–Fn14 pathway and certain cell-stress (UPR) responses can protect muscles in people with cancer-related or age-related wasting.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionUniversity of Houston NIH-funded
Lab location1 site (Houston, United States)
Project IDNIH-11260265 on NIH RePORTER

What this research studies

From a patient's perspective, researchers are studying why muscles shrink and weaken during cancer and aging by focusing on the TWEAK–Fn14 signaling system and the cell's unfolded protein response (UPR). They will use preclinical mouse models with muscle-specific removal of Fn14 and with targeted inhibition of UPR branches (PERK and IRE1/XBP1) to measure effects on protein synthesis, mitochondrial health, muscle mass, and strength. The team has reported that removing Fn14 or blocking parts of the UPR improves protein synthesis and reduces wasting in mice. Although the experiments are done in animals, the goal is to identify drug targets that could lead to future treatments for people with cachexia or age-related muscle loss.

Who could benefit from this research

Good fit: People with advanced cancer experiencing progressive muscle loss (cancer cachexia) and older adults with age-related muscle wasting are the patient groups most likely to be relevant to this research.

Not a fit: People without cancer- or age-related muscle wasting, or those whose muscle loss stems from unrelated causes, may not receive direct benefit, especially since most work is currently in animal models.

Why it matters

Potential benefit: If successful, this could point to new treatments that slow or reverse muscle wasting and help preserve strength and function in people with cancer or age-related frailty.

How similar studies have performed: Prior preclinical mouse studies, including work by this group, have shown promising results when Fn14 is removed or UPR arms are inhibited, but these approaches have not yet been tested in humans.

Where this research is happening

Houston, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions Advanced Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.