Pharmaceutics & Pharmaceutical Chemistry | College of Pharmacy
MICROENVIRONMENT EVOLUTION AND THERAPEUTIC CONSEQUENCES IN METASTATIC PROGRESSION
Shreya Goel, Assistant Professor
Metastases are responsible for a majority of cancer-related deaths. Inter-tumoral heterogeneity; the fact that every tumor has distinct genetic, epigenetic, and biophysical features, poses a challenge for effective cancer therapy. While genetic and epigenetic variants that influence a tumor’s response to targeted therapy have received great attention, comparatively less is known about the physiological heterogeneities in the metastatic TME. Aberrant blood vessels, hypoxia and dysregulated matrix, influence the delivery and hence, efficacy of administered chemo-, and immuno-therapies. Surprisingly, despite their critical roles in cancer progression, treatment response and resistance, our understanding of the vascular and stromal heterogeneities of metastatic TME remains limited.
The overarching goals of this project are to: (1) systematically catalogue the dynamic changes that occur in the vascular and stromal microenvironment of the metastatic tumors as they grow from single cell to micro- and macro-metastases, and (2) to evaluate how these changes correlate with and impact the delivery and therapeutic efficacy of clinical anti-cancer therapies.
We will evaluate these dynamic evolution of metastatic vascular and stromal niche in the context of experimental models of pulmonary metastases of triple negative breast cancer, with the expectation that findings from these studies will lead to multi-organ, multi-tumor investigations in advanced models of metastatic cancers.