Part 2: Breast Team
At the Center for Global Women’s Technologies (GWHT) our graduate students are working on three different projects; breast cancer, cervical cancer, and ethanol ablation. This week we want to tell you more about the Breast Team.
The Breast Cancer team has goals to address breast cancer in two different settings.
1. The focus in high resource settings is studying recurrence of breast cancer following therapy.
2. The focus in low resource settings is developing a better system for early and effective diagnosis of breast cancer.
American Cancer Society projections for 2020 list the breast as the leading cancer site for new cancer cases in females, estimating breast cancer to represent 30% of all new cases and 15% of cancer-related deaths. A leading cause of breast cancer deaths is due to tumor recurrence following therapy. These tumors can recur years, sometimes decades, after treatment from reservoirs of residual cells that persist in a dormant state.
To reduce the cancer burden, years of research have focused on several common biological signatures of cancer, deemed the Hallmarks of Cancer, including sustained growth, genetic mutations, resistance to cell death, and a deregulated metabolism, or the way cells use macromolecules for fuel.
Several recent studies have further reported that this last hallmark, metabolism, may be vital to understanding the underlying behavior of dormant and recurrent tumors. Tumors may rely on a wide range of energetic sources such as sugar, proteins, and fats. Once understood, these signature metabolic pathways can be leveraged as vulnerabilities and allow for the development of strategies to eliminate residual disease or prevent residual tumor cells’ subsequent reactivation into full recurrence.
Therefore, there is an unmet need for a method to study metabolism of the few, small populations of cancer cells that can survive as dormant cell populations over time.
Our group works to develop imaging platforms that can capture and establish metabolic and molecular signatures that report on a patient’s risk of developing recurrent disease. Specifically, we are interested in developing portable and low-cost technologies that can capture a tumor’s underlying behavior across a wide range of biological models.
— Dr. Megan Madonna (Assistant Director of Education for GWHT)
Targeting a tumor’s energy sources is a clinically actionable therapeutic approach, but identifying which tumors that are likely to respond remains difficult. Pinpointing how an individual tumor’s fuel preferences change from when it is a primary tumor, a dormant tumor, or a recurrent tumor can provide valuable information on a tumor’s aggressiveness or point towards targets of potential treatments.
While the rise of portable ultrasound and imaging systems have made it possible to provide point of care for breast cancer, in both high-resource and low-resource communities, there is a difficulty with receiving care because of pathology. Pathology is a branch of medical science that involves the study and diagnosis of disease through the examination of surgically removed organs, tissues (biopsy samples), bodily fluids, and in some cases the whole body (autopsy). (1).
In high-resource communities:
Pathology is easily accessible and able to be used for breast cancer diagnosis.
When a woman presents with a suspicious lesion on her mammogram, she undergoes diagnostic biopsy to determine what type of lesion is present by pathological analysis. (2)
Pathology requires a lot of labor and there is still a delay between time of diagnosis and time of treatment.
In low-resource settings:
These settings shoulder most of the total breast cancer burden and do not have the resources to perform standard-of-care treatments, which leads to higher mortality rates.
There is a scarcity of pathologists in fragile health care systems.
Despite its low specificity for distinguishing breast tumors from benign conditions, portable ultrasound systems are currently being used as a screening tool in lieu of mammography for breast cancer in LMICs. (3)
The challenge in low resource settings is early and effective diagnosis of breast cancer. Our team is addressing this issue of revamping effective diagnosis through the use of molecular diagnostics.
The CDC defines Molecular diagnostic testing as combining laboratory testing with the precision of molecular biology and has revolutionized the way clinical and public health laboratories investigate the human, viral, and microbial genomes, their genes, and the products they encode. (4)
We have ushered in an era of molecular diagnostics given the plethora of molecular targeting agents that have been developed for cancer treatment. We have harnessed this capability to make molecular diagnostics the potential new face of pathology.
— Dr. Nimmi Ramanujam
Our team is working on this by using a contrast agent, fluorescein, tethered to a small molecule inhibitor to heat shock protein 90 (HSP90), which is overexpressed in the different subtypes of breast cancer. We have designed a strategy to use portable microscopy to perform imaging, needle-based tissue excision and molecular diagnostics as a new strategy for breast cancer diagnostics at the point of care.
There is often significant patient attrition when multiple visits are required to diagnose and treat breast cancer in LMICs. Integrating diagnostics with an effective treatment strategy into a single visit will improve outcomes for patients in LMICs where standard of care pathology and surgical treatments are not feasible. (5)
Our Breast Team is hopeful to continue developing strategies that will save the lives of women in high-resource and low-resource communities. Learn more about the teams’ research by checking out some of their published research:
Optical imaging of glucose uptake and mitochondrial membrane potential to characterize her2 breast tumor metabolic phenotypes
In vivo optical metabolic imaging of long-chain fatty acid uptake in orthotopic models of triple negative breast cancer
Leveraging Surface Hsp90 Expression for Rapid-on-site Breast Cancer Diagnostics
In vivo metabolic imaging reveals mitochondrial membrane potential reprogramming following Her2-targeted therapy and dormant disease
Simultaneous in vivo optical quantification of key metabolic and vascular endpoints reveals tumor metabolic diversity in muring breast tumor models
Exploiting heat shock protein expression to develop a non-invasive diagnostic tool for breast cancer
Near-simultaneous quantification of glucose uptake, mitochondrial membrane potential, and vascular parameters in murine flank tumors using quantitative diffuse reflectance and fluorescence spectroscopy
Metaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging