Re: Johns Hopkins Dr. Sidransky on individualized therapy
Cancer is already in 3D conformation. Analyzing cultures of fresh tumor cells in "real life" 3D conformation makes profiling indicative of what willl happen in the body, where cells interact with and support other living cells, both malignant and non-malignant cells. That's why functional profiling studies cancer cells in small clusters or microspheroids.
Real-life cancers grow as a complex organism that includes both malignant and non-malignant components. It may include fibrous tissue, mesothelial cells, fibroblasts, endothelial cells, etc. In order to exhibit its most characteristic behavior patterns, a cancer cell needs to be surrounded by a colony of other cells, both normal and malignant.
Human tumors represent micro-ecosystems composed of transformed cells, stroma, fibroblasts, vascular elements, extra-cellular protein matrices and inflammatory elements. The behavior of human cancers and their reponse to therapy reflect the complex interplay between humoral, vascular, adhesion and cytokine-mediated events acting in concert.
Tumors are very complex organisms. Ignoring this complexity, most studies of human cancer in culture have focused upon individual tumor cells that have been removed from their complex microenvironoment. It needs to be kept intact.
Cells that are routinely broken up by mechanical and enzymatic means, alters their subsequent behavior. Some previous methods of assays limited their analysis only to isolated tumor cells and failed to incorporate the crucial contribution of non-tumorous elements to the cancer phenomenon.
When allowed to grow in vitro, living cancer cells develop into these tiny micro-spheroid clusters that form a complex biosystem in which each malignant cell reacts upon its fellow colonists in subtle but important ways.
Each of these microspheres contains all the complex elements of tumor biosytems that are found in the human body and which can impact clinical reponse.
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