Modulation of the Tumor Microenvironment

Nanomedicines are designed to target anti-cancer agents to the dynamic tumor microenvironment sparing healthy tissues from severe side effects and thereby enhancing therapeutic index of anti-cancer therapies. Nanoparticles extravasate into tumors through leaky and tortuous blood vasculature and are retained intratumorally for prolonged periods as the lymphatic system is absent or only poorly developed, a phenomenon referred to as Enhanced Permeability and Retention (EPR) effect. The physicochemical properties of nanoparticles such as size, shape, charge, and the nature of material they are made of play a major role in determining their fate in the body as well as within tumors. Despite an overwhelming therapeutic success of nanomedicines in preclinical tumor models, only a limited therapeutic benefit has been achieved in the clinical situation. One major concern in the clinic is the limited penetration of nanoparticles into tumors. In contrast to commonly used preclinical subcutaneous tumor models, clinical tumors are highly different due to the presence of fibrotic tumor stroma. Recent studies have acknowledged that penetration of nanoparticles in the target tissue and their accumulation at the tumor site is affected by many factors such as the characteristics of nanoparticles (size, charge, and shape), as well as the tumor microenvironment and intracellular signaling networks.

Evidence is increasing that tumor growth is not solely dependent on cumulative gene mutations, but also significantly influenced by the surrounding tumor stroma. Specifically, cancer cells co-exist in the tumor microenvironment with stromal components which is mostly comprised of fibroblasts, endothelial cells, inflammatory immune cells, adipocytes, and extracellular matrix (ECM). Complex interactions between tumor cells and the stroma govern tumorigenesis, tumor progression, and metastasis.

The research in the Prakash-Lab mainly focuses on three different types of cancer:

  1. Pancreatic Ductal Adenocarcinoma
  2. Glioblastoma Multiforme
  3. Mamma Carcinoma