Biomarker Predicts Treatment Efficacy in Triple-Negative Breast Cancer

Image: Figure 2: FACS analysis of various MDA-MB-231 Trop-2-transfectants and assessment of SG-mediated changes in Rad51 expression. 

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Biomarkers are any measurement in the body that can indicate disease, infection, or effects of the environment. These indicators are commonly used to reveal disease, but they can also be used to support ​​personalized cancer therapy.

“In recent years, there has been an increased focus on personalized cancer therapy [1]. One important aspect is the identification of key biomarkers that support a given treatment plan [1–5].”

Multiple biomarkers have been identified in breast cancers as helpful tools to guide targeted therapies, including the expression of HER2 and estrogen and progesterone receptors. In triple-negative breast cancer (TNBC), a number of distinct biomarkers have given rise to new targeted therapies, such as EGFR antibodies, AKT inhibitors, and PARP inhibitors.

In a well-read paper from Immunomedics, Inc. (recently acquired by Gilead Sciences, Inc.), researchers analyzed sacituzumab govitecan (SG; Trodelvy™) in TNBC. The team authored a research paper that was published by Oncotarget in 2020, and entitled, “Predictive biomarkers for sacituzumab govitecan efficacy in Trop-2-expressing triple-negative breast cancer.” To date, this paper has scored an Altmetric Attention score of 48. 

“Here we examined the potential role of biomarkers in predicting the efficacy of SG.”

The Study

Sacituzumab govitecan is an antibody-drug conjugate that targets human trophoblast cell-surface antigen-2 (Trop-2)ーwhich is a glycoprotein that is commonly overexpressed in many solid tumor types.

“Trop-2 is a 46 KDa transmembrane glycoprotein that is overexpressed on many solid tumor types and is correlated with an overall poor prognosis in patients, making it an attractive target for therapy [7, 9].”

The researchers examined a highly invasive and aggressive TNBC cell line (MDA-MB-231), which is not responsive to SG, and compared their findings to TNBC cell lines that are responsive to SG. Their goal was to determine how Trop-2 expression and the homologous recombination repair (HRR) pathway (through Rad51 expression) play roles in protecting the MDA-MB-231 cell line from SG mediated DNA damage. 

“Trop-2 expression levels as a positive, primary biomarker and HRR proficiency as a secondary, negative biomarker were assessed in vitro and in vivo.”

Trop-2 expression in transfected MDA-MB-231 and tumor xenografts were assessed, in vitro and in vivo Rad51 expression and DNA damage were assessed via western blot, and statistical analysis was carried out for data from in vivo therapy studies. 

Conclusion

Researchers found that high expression of Trop-2 was indeed a primary biomarker of SG efficacy. However, they note that further clinical trials will be needed to examine other secondary biomarkers that may also predict clinical benefit.

“To conclude, these data strongly support the hypothesis that as a biomarker, high surface Trop-2 expression on a patient’s tumor may be predictive of a positive clinical outcome for SG therapy.” 

Click here to read the full research paper, published by Oncotarget.

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