The tumor's extracellular environment is increasingly recognized as an important determinant for its progression and its response to therapeutics. TNBC tumors are highly secretory in nature and usually have very rich microenvironment due to high tumor infiltrates. It has been shown recently that therapeutic agents not only induce molecular reprograming inside the cells but also re-orchestrates the autocrine and paracrine tumor secretome which eventually affects the response to therapy.
We intend to identify and functionally examine the TNBC subtype-specific secretome and its therapy-induced reprograming that might regulates therapeutic outcome in TNBC patients. Utilizing cellular and clinically driven models that represent chemo-naïve, chemo-responsive and chemo-tolerant variables, we are trying to identify “secretomic-signatures” that can predict the outcome of TNBC patients before and under treatment. Some of those secretomic components can potentially be utilized for therapeutic targeting due to their strongly established intracellular molecular networks that nurture maintenance of drug-tolerant persister states in TNBC cells.