Breakthrough in Cancer Monitoring

UHCOP's Trivedi Earns HOPA Literature Award for First-time Detection of Elusive Tumor Cells in Breast Cancer Patient-derived Xenograft Mouse Model

A UH College of Pharmacy faculty researcher's publication on the first-ever detection of two elusive types of cancer cells in xenograft-bearing mouse models – a discovery that could increase understanding of how the cancer spreads to other parts of the body – has been recognized by the Hematology-Oncology Pharmacy Association.

The paper by UHCOP Assistant Professor Meghna V. Trivedi, Pharm.D. ('03), Ph.D. ('04), BCOP, and her colleagues from Baylor College of Medicine, including her co-senior author Rachel Schiff, Ph.D.; University Federico II (Naples, Italy); and Harvard Medical School earned HOPA's 2016 Basic Science and Clinical Research Literature Award at the 12th HOPA Annual Conference on March 17 in Atlanta.

The paper, entitled "Circulating and Disseminated Tumor Cells from Breast Cancer Patient-derived Xenograft-bearing Mice as a Novel Model to Study Metastasis," was published in a 2015 issue of the peer-reviewed journal Breast Cancer Research.

Trivedi and her colleagues have been investigating experimental models that could provide a renewable, continual source of two types of cancer cells – circulating tumor cells (CTCs) in blood and disseminated tumor cells in bone marrow (BM-DTCs) – that have been associated with cancer metastases, particularly in breast cancer patients.

“We found an association between the presence of CTCs and BM DTCs found in the mice bearing the patient-derived xenografts, which is also observed in patients, further validating the utility of these models," Trivedi said. "More importantly, we found a correlation between the presence of CTC clusters and lung metastasis. This was quite interesting as these clusters are observed in some patients, and no outcome has been linked to the presence of CTC clusters.”

With this discovery, Trivedi and her team are continuing to explore the possibility that CTCs could serve as a valuable biomarker to help guide therapeutic decisions.

To date, the utility of CTCs and BM-DTCs have been impractical due the biophysical limitations: CTCs are generally not present in high enough quantities in a typical blood sample, and fluid extracted from bone marrow not only fails to yield sufficient quantities of DTCs but also is hindered by accessibility challenges and potential complications in the patient.

"The tumor biology is continuously changing, so CTCs represent what's going on in the tumor of patients at that particular time," Trivedi said. "Collection of some blood is much easier than getting another biopsy of tumors."

The team also conducted gene expression analysis to identify a gene signature of the primary tumor predictive for both CTC clusters and lung metastases in the patient-derived xenograft lines.

"We identified a four-gene signature overlap, which we compared against a public datasets of breast cancer patients and found that this gene signature predicted worse distant metastases-free survival in breast cancer patients," Trivedi said. "This development offers a new investigative and preclinical models for evaluating prospective therapies.

"These transplanted tumor cells and their multi-generational successor tumor cells retain the molecular and biological characteristics of the parental tumor cells, which gives us confidence that these models represent a clinically-relevant tool for studying CTCs and their role in tumor progression and metastases and their utility in making treatment decisions."

Another area the investigators would like to explore further is the biology of CTC clusters, which some research has suggested may provide further links to how cancer cells spread and proliferate throughout the body.