R01CA260196

Mechanistic Understanding of the Lifecycle of a Circulating Hybrid Cell - 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 the 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 the potential to influence the 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 stage II and late-stage colorectal cancer cohorts supports analyses across the disease axis, with an emphasis on stage II CRC patients with undetected micrometastases at the time of diagnosis. Evaluation of the lifecycle of the hybrid cell from the primary tumor to dissemination will provide biological insight into the metastatic process with great potential to impact the management and care of patients with cancer.

Oregon Health & Science University

TO PROVIDE FUNDAMENTAL INFORMATION ON THE CAUSE AND NATURE OF CANCER IN PEOPLE, WITH THE EXPECTATION THAT THIS WILL RESULT IN BETTER METHODS OF PREVENTION, DETECTION AND DIAGNOSIS, AND TREATMENT OF NEOPLASTIC DISEASES. CANCER BIOLOGY RESEARCH INCLUDES THE FOLLOWING RESEARCH PROGRAMS: CANCER CELL BIOLOGY, CANCER IMMUNOLOGY, HEMATOLOGY AND ETIOLOGY, DNA AND CHROMOSOMAL ABERRATIONS, TUMOR BIOLOGY AND METASTASIS, AND STRUCTURAL BIOLOGY AND MOLECULAR APPLICATIONS.

93.396 - Cancer Biology Research

National Cancer Institute (NCI) [HHS - NIH]

Portland, Oregon 972393011 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 398% from $632,739 to $3,151,928.