Targeting USP27X to lower Cyclin D1 in HER2 therapy–resistant breast cancer

The role of USP27X-Cyclin D1 axis in HER2 Therapy Resistant Breast Cancer

NIH-funded research Roswell Park Cancer Institute Corp · NIH-11295402

This work looks at blocking the protein USP27X to reduce Cyclin D1 and help people with HER2-positive breast cancers that have stopped responding to HER2 drugs.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionRoswell Park Cancer Institute Corp NIH-funded
Lab location1 site (Buffalo, United States)
Project IDNIH-11295402 on NIH RePORTER

What this research studies

Researchers are studying how the enzyme USP27X keeps Cyclin D1 levels high in HER2-positive breast cancers that resist therapy. In the lab they reduce USP27X and watch whether Cyclin D1 falls and cancer cells become more sensitive to HER2-targeted and CDK4/6 drugs. They use cell models and mouse xenografts and link USP27X levels to patient outcomes to guide target selection. The goal is to find a way to drive Cyclin D1 degradation so tumors that no longer respond to HER2 therapy can be treated more effectively.

Who could benefit from this research

Good fit: Patients with HER2-positive breast cancer that is refractory or recurrent after HER2-targeted therapy, especially those whose tumors show Cyclin D1 (CCND1) amplification or high USP27X expression, would be the likely candidates.

Not a fit: People with non–HER2 breast cancers or tumors without Cyclin D1 overexpression are unlikely to benefit from this targeted approach.

Why it matters

Potential benefit: If successful, this approach could restore drug sensitivity and improve treatment options for patients with HER2-positive breast cancer that no longer respond to current HER2 therapies.

How similar studies have performed: Indirect targeting of Cyclin D1 pathways (for example with CDK4/6 inhibitors) has clinical benefit, but directly targeting USP27X is a new, preclinical strategy that has shown promising results in lab and mouse models.

Where this research is happening

Buffalo, 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.
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.