CDRI scientists find new option to tackle Triple-Negative Breast Cancer metastasis

India is known as the Triple-Negative Breast Cancer (TNBC) capital of the world owing to its high incidence

A team of scientists from Lucknow-based Central Drug Research Institute (CDRI), a CSIR Laboratory, has demonstrated a new and viable mechanism to tackle Triple-Negative Breast Cancer (TNBC), which is the deadliest among all breast cancer subtypes with few therapeutic options.

The CSIR-CDRI research team led by Dipak Dutta has recently published an article in a peer-reviewed international journal, ‘Nature Communications’ that uncovers new functions for epigenetic modulator EZH2 (Enhancer of Zeste homolog 2) in the spread (metastasis) of TNBC. An epigenetic modulator regulates whether a gene will be expressed or not.

Using an inhibitor of EZH2, Tazemetostat, Datta and his team have demonstrated a new and interesting mechanism for EZH2-mediated gene upregulation that can dictate TNBC progression.

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According to the study, in contrast to its classical role in suppressing gene expression, EZH2 could mediate the overexpression of specific genes, promoting the spread of cancer from the breast to the liver and spleen in animal models of TNBC. These findings suggest a rationale for targeting TNBC with EZH2 inhibitors.

India is known as the TNBC capital of the world owing to its high incidence. This type of cancer is associated with early metastasis resulting in poor five-year survival rates.

The study said that the incidence of TNBC was higher (18-31 per cent) in India compared to other regions of the world (8-15 per cent). The high rate of TNBC in India is linked to several risk factors, the most important of which are lifestyle changes, obesity, a family history of the disease, a high mitotic index, and BRCA1 gene mutations.

Another important aspect is that TNBC is more prevalent among younger women.

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Unlike other types of cancer for which therapies that specifically target the mutated pathways exist (targeted therapies), for TNBC, routine chemotherapy is the only treatment option. Such therapies are associated with several side effects such as tiredness, hair loss, anaemia etc. Moreover, in a majority of the cases, it fails to deliver long-term benefits to the patients. Therefore, there is a dire need for the discovery of targeted therapy against this deadly breast cancer subtype.

The current study discovers one of the therapeutic vulnerabilities of TNBC which is the functional hyperactivation of epigenetic modulator EZH2 that regulates TNBC spread from the breast to the liver and spleen. Therefore, inhibition of EZH2 function by FDA approved EZH2 inhibitor drug Tazemetostat (EPZ6438) could be a viable option to tackle TNBC metastasis in the clinic.