# Rapid analysis of patient tumor cell drug responses to reduce metastatic risk

> **NIH VA I01** · BALTIMORE VA MEDICAL CENTER · 2024 · —

## Abstract

Rapid analysis of patient tumor cell drug responses to reduce metastatic risk
 Background: The current limitations of clinical cancer imaging prevent a clear understanding of how drugs
aimed at cell growth affect the metastatic potential of circulating tumor cells (CTCs) in breast cancer
patients. With more than 2.2 million female Veterans, the current incidence of breast cancer predicts that at
least 275,000 female Veterans will confront breast cancer treatment and require effective treatments that
minimize the risk of lethal metastatic spread. Recent advances in CTC analysis have shown that clusters of
breast cancer CTCs have up to 50x higher metastatic potential. The Martin lab discovered unique
microtentacles (McTNs) on the surface of breast tumor cells that increase cluster formation, and are indicative
of the elevated stem cell characteristics that promote breast cancer metastasis. Current cancer therapies that
stabilize tubulin (like taxanes and epothilones) can increase McTNs, stem cell characteristics, tumor cell
clustering, and reattachment. These results emphasize the need to clarify how current drugs affect free-floating
tumor cells so that therapies can be better tailored to individual patients and reduce long-term metastatic risk.
 Objective/Hypothesis: Bringing together a multidisciplinary team of tumor cell biologists, bioengineers,
and breast cancer clinicians; the objective of this project is to use a novel microfluidic device to rapidly image
free-floating breast tumor cells and define 3 phenotypes that are predictive of metastatic potential (McTNs,
sphere formation, clustering) and key molecular markers. These phenotypes and molecular profiles will be
related to metastatic potential and drug response using clinically-relevant PDX transplants in mice. This study
will test the hypothesis that key functional phenotypes and molecular markers of freshly-isolated breast tumor
cells can serve as immediate indicators of metastatic potential and provide a platform to rapidly test the
responses of individual patient tumor cells to cancer drugs.
 Specific Aims:
 1) Optimize microfluidic cell tethering to measure 3 functional phenotypes of metastatic potential.
 2) Establish molecular framework for tumor cell drug responses in patient-derived xenograft (PDX) cells.
 3) Define shared molecular and functional characteristics of fresh patient tumor cells, PDX and CTCs.
 Methods: This project will use confocal microscopy to examine 3 phenotypes (McTNs, sphere formation,
and clustering) in breast tumor cell lines and a panel of existing patient-derived xenografts (PDX) supplied by
the Translational Core Laboratory at the University of Maryland Greenebaum Cancer Center. In parallel, we
will collect fresh patient tumor samples to compare molecular markers and phenotypes in the fresh cells with
the PDX that eventually grow in mice. PDX recapitulate the metastatic behavior of the patient’s original tumor
far more faithfully than any tissue culture...

## Key facts

- **NIH application ID:** 10929944
- **Project number:** 5I01BX002746-06
- **Recipient organization:** BALTIMORE VA MEDICAL CENTER
- **Principal Investigator:** STUART S MARTIN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929944

## Citation

> US National Institutes of Health, RePORTER application 10929944, Rapid analysis of patient tumor cell drug responses to reduce metastatic risk (5I01BX002746-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10929944. Licensed CC0.

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