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Exclusive Target for Triple-Negative Breast Cancer Treatment Identified

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Researchers from University of California, Berkeley strategized an innovative approach and identified Glutathione-S-transferase Pi 1 (GSTP1) as the novel, weak spot of the Triple-negative breast cancer (TNBC) to hunt it down. TNBC is one of the most dreadful forms of breast cancer.

Researchers used “reactivity-based chemoproteomics” technique which leads them to that potential target on the specific proteins which are responsible for the functioning and growth of the TNBC tumor cells and this approach could lead to more precise drug development strategies. The study is published in Cell Chemical Biology.

 

The Eureka moment

Researchers were delighted to notice that a single, unique target – GSTP1 was all they were looking for.

GSTP1 is the only metabolically active enzyme that specifically expresses itself more in TNBC compared to other breast cancers. GSTP1 is the driving force behind the TNBC cell metabolism and functioning.

Glycolysis in TNBC cells are regulated by GSTP1 which is essential for the functioning of the cancer cells. Therefore, inhibition of GSTP1 will lead to the collapse of the glycolytic metabolism in TNBC cells ultimately leading to starvation of cells and loss of its signalling capability for tumor growth.

 

Researchers sharpened the arrow!!!

A molecule named LAS 17 was developed by Eranthie Weerapana, co-author and associate professor of chemistry at Boston College. LAS 17 bind specifically to the target site on the GSTP 1 molecule tightly and reversibly leading to the inhibition of its enzyme activity. During the study of LAS 17 on mice, no toxic side effects were observed.

GSTP1 in triple negative breast cancer

Figure 1.  The metabolic pathway involved in the TNBC cell metabolism and functioning. (Photo credit: Louie et al., DOI: //dx.doi.org/10.1016/j.chembiol.2016.03.017)

Earlier, they have also worked on the interaction of specific chemical probes with two amino acids-cystine and lysine which has been found to be involved in important structural and functional transitions that promotes TNBC development. In a study led by Luika Timmerman in University of California, San Francisco, FDA-approved anti-inflammatory drug called sulfasalazine were used to block a specific cystine transporter- xCT on tumor cells.

 

Take a look at the foe 

TNBC is that form of breast cancer in which the genes for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are not expressed. It makes the disease more aggressive and difficult to treat as most of the chemotherapies target one among these three receptors. Therefore, combination of therapies like surgery, neoadjuvant chemotherapy or radiation therapy is given as a standard treatment.

10-20% of the breast cancers diagnosed is TNBC.

In the expedition to look for the specific receptor and development of therapy, various targeted therapies like poly ADP-ribose polymerase (PARP) inhibitors, vascular endothelial growth factor (VEGF) inhibitors, epidermal growth factor (EGFR)-targeted therapies are under research.

The discovery of the function of GSTP 1 in TNBC is a huge success which can lead to a speedy development of effective therapy for this dreadful breast cancer. It has dwarfed the conventional strategies of TNBC therapeutic research and could catapult the TNBC research and development activity much farther.

Featured image credit: Close-up View Of A Cancer Cell © LexxIam (Stock Photo ID: 81350981)

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