Keywords
1. Microfluidic assay
2. Breast cancer metastasis
3. Cell motility proliferation
4. Antimetastatic therapeutics
5. Patient-derived xenografts
In a striking advancement in the fight against breast cancer, researchers from The Johns Hopkins University and the Marlene and Stewart Greenebaum National Cancer Institute Comprehensive Cancer Center have developed a microfluidic assay that could significantly improve the management of breast cancer by predicting the likelihood of metastasis in patients, paving the way for personalized treatment regimens and rapid screening of potential antimetastatic drugs. Published in the prestigious journal Nature Biomedical Engineering, the study describes a groundbreaking methodology that quantifies the abundance and proliferation index of migratory cells within tumor samples, aimed at identifying the metastatic potential of cancers derived from breast tissue.
DOI: 10.1038/s41551-019-0400-9
The Challenge of Metastasis Prediction
Breast cancer remains a leading cause of cancer-related deaths among women, with metastasis to distant organs being the primary factor contributing to mortality. Predicting which breast cancer patients will develop metastases has been historically challenging, leading to overtreatment in patients with benign diseases and insufficient treatment in those with aggressive cancers. The latest innovation from Konstantopoulos et al., supported by significant funding from the National Institutes of Health (NIH), can potentially transform clinical approaches by accurately identifying individuals at high risk for distant metastasis.
The Microfluidic Assay: A Deep Dive into the Technology
The microfluidic device, developed by Christopher L. Yankaskas and his team, isolates highly motile cells from breast cancer specimens. This subpopulation of cells is believed to play a pivotal role in cancer dissemination. By analyzing these migratory cells, the device can predict the likelihood of tumor spread with a high degree of accuracy. Remarkably, the microfluidic assay demonstrated that highly motile cells displayed not only similar tumorigenic potential but also a significantly higher propensity for metastasis in comparison to unsorted cancer cells when assessed in vivo.
RNA sequencing of the migratory cells further revealed that these cells were enriched with genes associated with cell movement and survival, underscoring the potential mechanisms of metastasis at the genomic level. Such insights could lead to better therapeutic strategies targeting these specific pathways.
Implications for Customized Patient Care
This innovative tool represents a leap forward in precision medicine, enabling clinicians to tailor treatment regimes based on the metastatic potential of a patient’s tumor. It provides a functional assay that complements genetic testing and can be incorporated into existing diagnostic workflows to enhance patient care. For instance, according to the authors, the assay may serve as a companion diagnostic tool for selecting the most effective treatment options for individual patients, mitigating the risk of over or undertreatment.
Integrating the microfluidic assay into clinical practice could also lead to the reevaluation of current treatment protocols, as seen in the implementation of radiotherapy guidelines for locoregional breast cancer recurrences (Harms et al., 2016). Moreover, combining the assay’s capability with existing genomic analyses, such as the multigene assay used to predict recurrence in tamoxifen-treated, node-negative breast cancer (Paik et al., 2004), might refine prognosis and therapeutic decision-making.
Rapid Screening of Antimetastatic Therapeutics
The quest for effective antimetastatic drugs has been ongoing, with the need for high-throughput and reliable screening methods. The microfluidic assay offers a rapid and precise approach to evaluating potential drug candidates that could inhibit or decrease the metastatic spread of breast cancer cells. It could facilitate the early-phase clinical trials, potentially expediting the discovery of promising new treatments that challenge metastasis at its roots—cell motility and proliferation.
Prospects and Reflections
Although this study represents a significant milestone in the context of breast cancer management, it is the beginning of a journey. In light of personalized medicine, this assay opens new frontiers in our ability to understand and treat breast cancer proactively and precisely. Yet, the translation of these findings into routine clinical practice will require extensive validation through clinical trials and concerted efforts to integrate such innovations into healthcare systems seamlessly.
The potential cost-effectiveness of integrating the microfluidic assay into standard practice could also be substantial, echoing findings similar to those reported by Chandler et al. (2018), which looked at the cost-effectiveness of gene expression profile testing in community practice. Cost reductions stem from avoiding unnecessary treatment while ensuring aggressive therapies for patients who would benefit the most, underscoring how technological advances serve not only clinical objectives but also economic sustainability in healthcare.
Conclusion
The development of the microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens stands as a testament to the relentless pursuit of better cancer management strategies. With its foundation firmly rooted in rigorous scientific research, the promise of this technology extends beyond the laboratory bench to real-world clinical applications that could save lives and streamline cancer care.
References
1. Yankaskas, C. L., Thompson, K. N., Paul, C. D., Vitolo, M. I., Mistriotis, P., Mahendra, A., et al. (2019). A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens. Nature Biomedical Engineering, 3(6), 452–465. https://doi.org/10.1038/s41551-019-0400-9
2. Steeg, P. S. (2016). Targeting metastasis. Nature Reviews Cancer, 16, 201–218. https://doi.org/10.1038/nrc.2016.25
3. Siegel, R. L., Miller, K. D., & Jemal, A. (2018). Cancer statistics, 2018. CA: A Cancer Journal for Clinicians, 68, 7–30. https://doi.org/10.3322/caac.21442
4. Harms, W., Herkstroter, M., & Sroka-Perez, G. (2016). DEGRO practical guidelines for radiotherapy of breast cancer VI: therapy of locoregional breast cancer recurrences. Strahlentherapie und Onkologie, 192, 199–208. https://doi.org/10.1007/s00066-016-0951-6
5. Paik, S., Shak, S., Tang, G., et al. (2004). A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. New England Journal of Medicine, 351, 2817–2826. https://doi.org/10.1056/NEJMoa041588
6. Chandler, Y., Scheibling, C., Holleczek, B., Jäger, C., & Hof H. (2018). Cost-Effectiveness of Gene Expression Profile Testing in Community Practice. Journal of Clinical Oncology, 36(6), 554–562. https://doi.org/10.1200/JCO.2017.75.8753