Neo-adjuvant chemotherapy is the mainstay treatment for TNBC patients. There has been growing evidences that the response to chemotherapeutic agents in TNBC is very variable and uncertain, which cannot be explained or categorized on the basis of somatic or genetic variations. Moreover, drug resistant and relapsed TNBC rarely show any additional genetic mutations, which ascertains that the drug resistance is primarily driven by epigenetic reprograming in the tumor cells. This has been demonstrated that some cells in solid tumors attain drug-tolerant persister state that act as reservoirs for disease relapse and drug resistant. Persister cellular states are purely driven on transient molecular reprograming in cancer cells that can be epigenetic in nature.
We are attempting to identify specific and novel epigenetic molecules that are responsible for deriving chemotherapy resistant states in TNBC subtypes using molecular and pharmacological High-throughput (HTP) screening methods. Specific targets and their functional characterization in cellular and pre-clinical models together with their precise mapping in human TNBC tumors utilizing bioinformatics approaches and tumor tissue based probing will ascertain their role in drug resistance. This approach is expected to identify and target the epigenetic determinants of drug resistance and restore the chemosensitivity in TNBC.