Treatment approach may eradicate triple-negative breast cancer.
In a new study, researchers have created a new way to eradicate aggressive types of breast cancer, such as triple-negative breast cancer (TNBC), which has no targeted treatments available.
Recently, it has been found that oncogene MYC is elevated in TNBC. This discovery has the potential to develop targeted therapies that would selectively kill MYC-overexpressing TNBC cells.
According to the study, published by the US Department of Defense Congressionally Directed Medical Research Programs, researchers used a fluorescence activated cell sorting (FACS) assay to quarantine disseminates tumor cells (DTCs) from patient-derived xenograft models (PDX) of breast cancer. DTCs are cancer cells that reside in peripheral tissue and have the potential to develop into metastatic tumors.
Using FACS, researchers sorted cells based on the expression of CD298, which allowed early detection of early DTCs and DTCs from late stage metastatic tumor-burdened tissues. The researchers wrote the genetic signatures of isolated cells could be determined by qPCR.
Metastatic cells from low tumor-burdened tissues were discovered to have stem-cell like gene structures. Cells from high-burdened tissues have signatures similar to the primary tumor.
According to the study, cells from low-burdened tissues were dormant, while cells from high-burdened tissues showed signatures of luminal differentiation, suggesting they entered the cell cycle and expressed a high level of MYC.
DTCs from high-burdened tissues were seen to be sensitive to dinaciclib, a cyclin-dependent kinase inhibitor. After 4 weeks, DTCs were only seen in 1 of the 24 mice who received dinaciclib compared with 11 of 25 vehicle-treated mice.
Researchers noted that diniciclib had a greater effect on metastatic tumors rather than primary tumors, since many of the mice had substantial primary tumors at the end of the study.
The results suggest that treatment with CDK 1/2/5/9 inhibitors can stop tumor-initiating cells and diniciclib can prevent metastatic breast cancer through the elimination of DTCs with high MYC expression.
Researchers used metabolomics in the second part of the study and found that fatty acid oxidation (FAO) intermediates as upregulated in a MYC-driven model of TNBC, according to the study.
Inhibition of FAO decreased energy metabolism and blocked tumor growth in both the MYC-driven transgenic TNBC model and the MYC over-expressing TNBC PDX model.
Researchers concluded the findings suggest that FAO has an important role for tumor activity and further research needs to be conducted.