Grant: Operating Grant

We aim to identify materials that favor or suppress growth of cancer stem cells (CSC). These cells are hypothesized to be at the origin of many cancers. They are resistant to drugs and radiation treatment and a few CSCs surviving the treatment could re-initiate the growth of the tumor. Recent data suggest that non-stem and stem cancer cells can readily interconvert. Eradication of CSC, thus, might not eradicate the tumor if the environment in the tumor favors re-appearance of stem cells. We hypothesize that eradication of cancer cells could be improved by a therapeutic biomaterial that can prevent re-emergence of CSCs and, thus, minimize the relapse of cancer. Toward this goal, we start from synthetic materials that favor growth of CSC; we have the first evidence for the existence of such material. We observed that breast cancer cells growing on surfaces modified by specific peptide sequence which targets TGF-beta-receptor enrich a population of CSC after only 4 days of culture. While this material itself is not the therapeutic solution, it is an important practical and fundamental starting point. First, it allows for culture of CSC in sufficient quantities for research and drug screening. In our proposal, it provides a supply of CSC to identify a material that has the opposite action. In the second part of the proposal, we aim to identify materials that rapidly decrease the fraction of CSC in the population. We synthesized a large array of materials displayed on one surface; seeding the CSC-rich population of cells and counting the number of CSC over time will allow us to identify material with the desired properties. Through iterative testing, we aim to find material that diminishes CSC population; we will validate its potential therapeutic action by co-implanting this material and cancer cells in a mouse host. Such material, combined with other anti-cancer therapies, could provide decrease in local re-occurrence of cancer after eradication of cells.