# Mechanistic understanding of the lifecycle of a circulating hybrid cell

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $605,359

## Abstract

Metastatic disease accounts for >90% of cancer-related deaths worldwide, yet this phase of tumor progression
is the least biologically understood. The consequence of this lack of knowledge is that we do not have the
appropriate therapeutic arsenal to defeat metastatic cancer. New revelations for colorectal cancer point to shed
neoplastic cells into peripheral blood even from early stage tumors, suggesting this is why some early stage
tumors recur despite seemingly successful treatment. However, whether all early stage primary tumors shed
neoplastic cells, or if only subsets of more aggressive neoplastic cells garner ability to disseminate is not known.
This highlights the critical gap in knowledge of the mechanisms underlying neoplastic cell dissemination leading
to distant disease. Identifying the key features within the lifecycle of a disseminated tumor cell will unravel this
important step in tumor progression with potential to influence management of cancer care. Our study leverages
newly developed state-of-the-art phenotypic analyses of key attributes of a recently discovered neoplastic hybrid
cell in primary tumors and in peripheral blood, termed circulating hybrid cells (CHCs), supported by cutting-edge
computational analyses. Interestingly, CHCs harbor tumor-initiating properties implying that they have high
potential as effectors of metastatic tumor seeding. We will detail cells poised to disseminate from the primary
tumor into circulation and seed metastatic sites combining protein, multi-omic analyses and functional behavioral
analyses. A focus on a stage II and late stage colorectal cancer cohorts support analyses across the disease
axis, with an emphasis on stage II CRC patients with undetected micrometastases at the time of diagnoses.
Evaluation of the lifecycle of the hybrid cell from primary tumor to dissemination will provide biologic insight into
the metastatic process with great potential to impact the management and care of patients with cancer.

## Key facts

- **NIH application ID:** 10851989
- **Project number:** 5R01CA260196-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Summer Lynne Gibbs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $605,359
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851989

## Citation

> US National Institutes of Health, RePORTER application 10851989, Mechanistic understanding of the lifecycle of a circulating hybrid cell (5R01CA260196-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10851989. Licensed CC0.

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