GrantR21National Cancer Institute
Deconstructing the heterogeneity of cancer-associated muscle wasting
- Activity
- R21
- Institute
- National Cancer Institute
- Fiscal years counted
- 2026
- Amount counted
- $390,549
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Abstract public domain (NIH RePORTER)
ABSTRACT Skeletal muscle wasting affects up to 80% of patients with advanced cancer and directly impacts surgical prognosis, chemotherapeutic response, morbidity, mortality, and quality of life. Treatment options for patients experiencing cancer-associated muscle wasting/cachexia are limited. Our long-term goal is to develop and leverage a detailed molecular understanding of skeletal muscle wasting to identify novel treatment paradigms that limit lean mass loss in cancer patients. A major obstacle contributing to poor translation of pre-clinical findings to patients is the relatively small number of experimental models that often fail to recapitulate key aspects of the human condition. We present preliminary data highlighting the strengths of using patient-derived organoids (PDOs) to model pancreatic cancer diversity (e.g. clinical characteristics, tumor genetics, molecular subtypes) as well as their use to study cancer-associated muscle wasting. In response to PAR-25-139, the central goal of this proposal is to develop and use PDOs as clinically relevant tools to study and target cancer- associated muscle wasting. We will achieve this goal by completing the following objectives: 1) we will query atrophy induction/muscle wasting phenotypes in vitro and in vivo through a lens of cancer subtype heterogeneity, and 2) we will define and target PDO-specific wasting programs. Successful completion of these objectives will be a significant step towards bridging the gap between discovery/translational science and clinical research that benefits PDAC patients.
Public health relevance public domain (NIH RePORTER)
NARRATIVE The long-term goal of our group is to develop and characterize interventions designed to combat cancer- associated muscle loss, thus improving patient outcomes and quality of life. The proposed studies aim to leverage patient-derived organoids (PDOs) to better study and target patient and tumor heterogeneity.