Triple negative breast cancer and synthetic lethality
Abstract
Triple negative breast cancer (TNBC) is a unique type of breast cancer characterized by the lack of expression of estrogen receptors (ER), progesterone receptors (PR) and the human epidermal growth factor receptor 2 (HER2). TNBC is a heterogeneous disease and in general is known for its aggressive nature, distinct metastatic patterns and lack of known target therapies. In the search of new therapeutic targets few have been proven to be successful however one of significance involves the concept of synthetic lethality. An interaction is considered synthetically lethal when a mutation occurs within a protein who is characterized as cancer specific and the tumor cell requires the activity of the synthetic lethal partner for gene viability. Some examples of synthetically lethal interactions within TNBC involve PARP inhibitors and the overexpression of the MYC pathway. Screening for synthetic lethality can be done using RNA interference, CAS9 libraries, and chemical screening. Applying these concepts to TNBC a screen was proposed in order to find a synthetic lethal interaction in the subtype of TNBC, Infiltrating Ductal Carcinoma.
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