A major contributing factor to mortality in cancer patients is relapse after therapy, and developing resistance. Cancer recurrence and resistance is related to the existence of a very small population of initiating stem cells (CSCs) in the tumor tissue with high expression of ATP-binding cassette (ABC) transporter proteins associated with drug resistance. After therapy, the bulk of tumor shrinks to <1% of its initial volume and the tissue becomes enriched with CSCs that are highly resistant to therapies. Further, as much as 40% of the volume of solid tumors is occupied by tumor-associated macrophages (TAMs), specifically immunosuppressive M2-macrophages, which play a central role in cancer progression. In my presentation, I will present a 3D co-culture system consisting of enriched CSCs and TAMs as a platform for preclinical drug screening and toxicity evaluation against the most aggressive cell colonies in the population of cancer cells. Using this novel 3D drug screening platform, we discovered that TAMs phenotype changes when co-cultured with CSCs and TAMs release factors that promote CSC maintenance. I will also discuss in my presentation the role of nanoparticles in overcoming resistance to drug uptake by cancer stem cells co-cultured with TAMs.
Audience take away:
• Cancer stem cells control the phenotype of TAMs
• TAMs contribute to the niche for maintenance of stemness in cancer cells
• TAM-CSC tumor model as a preclinical drug efficacy platform
• Nanoparticles can overcome resistance to drug delivery to cancer stem cells