A Novel Approach Utilizing Organ Specific Age Proteomics

Last updated: January 23, 2025
Sponsor: UNC Lineberger Comprehensive Cancer Center
Overall Status: Active - Recruiting

Phase

N/A

Condition

Breast Cancer

Cancer

Treatment

organ-specific protein signatures assessment

p16INK4a mRNA level assessment

Clinical Study ID

NCT06789653
LCCC2435
  • Ages 22-66
  • Female

Study Summary

This study compares changes in P16INK4A expression and plasma proteomic signatures of specific organ age pre- and post-chemotherapy in women treated with adjuvant chemotherapy for early-stage breast cancer. It aims to determine if biological and accelerated immune aging, assessed using T cells from peripheral blood, represents aging in different organs.

Patients receiving chemotherapy, especially adjuvant regimens that include anthracyclines and taxanes, often experience late development of cardiac toxicity, functional loss, and cognitive decline. Comparing baseline characteristics with organ aging before therapy might identify patients at the highest risk for chemotherapy complications. For example, this is clinically significant for patients whose therapy includes taxanes or other drugs known to cause peripheral neuropathy. Identifying aging in the neurological or vascular systems before treatment might lead to changes in regimens.

Determining accelerated aging in specific organs allows for investigating interventions to mitigate organ damage. For instance, identifying patients at the highest risk of cardiac aging after treatment could lead to testing the effects of exercise, senolytics, and other strategies to reduce the risk of long-term heart disease.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Age ≥22years and <66 years

  • Diagnosed with early-stage breast cancer (The American Joint Committee on Cancerstages I-III).

  • Understand and read English.

  • Receive care at the study site.

  • Able to understand and participate in study procedures for length of study.

Exclusion

Exclusion Criteria:

  • Unable to provide consent, unable to communicate verbally.

  • Unable to understand or read English.

  • Enrolled in hospice care.

Study Design

Total Participants: 60
Treatment Group(s): 2
Primary Treatment: organ-specific protein signatures assessment
Phase:
Study Start date:
October 10, 2024
Estimated Completion Date:
August 01, 2026

Study Description

Chemotherapy has revolutionized cancer treatment, significantly improving relapse-free and survival rates for many cancers. However, these advances have come with a downside, and nowhere is this more evident than in childhood cancer. Despite the significant advances in the curability of most childhood cancers, up to 20% of patients die of comorbidity and secondary cancers by the age of 35 years.

Recent research shows that a plasma proteomic measure of protein abundance and expression can provide a" global" proteomic signature that accurately predicts chronologic age in the general population. It was shown that accelerated organ aging conferred a 20-50% higher mortality risk, and this was pronounced for those with accelerated cardiac and brain aging.

Previous studies have shown that p16INK4a, a robust biomarker of cell senescence measured in peripheral blood T cells, rises dramatically and likely irreversibly after adjuvant therapy for breast cancer. For anthracycline regimens, p16INK4a changes suggest 10 to 20 years of accelerated aging shortly after treatment. Additionally, in murine models, changes in P16INK4A are seen in all organs as mice age, but not all organs age at the same rate.

Connect with a study center

  • University of North Carolina

    Chapel Hill, North Carolina 27599
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.