Complex Elements of Tumor Biosystems

Tumors contain lots of types of cells and that's why the functional profiling platform has recognized interplay between cells, stroma, fibroblasts, vascular elements, cytokines, macrophages, lymphocytes and other extracellular material.

This has lead to the focus on the human tumor primary culture microspheroid (microclusters), which contains all of these elements. The functional profiling platform studies cancer response to drugs within this microenvironment, enabling it to provide clinically relevant predictions to cancer patients. It is their capacity to study human tumor microenvironments that distinguishes it from other platforms in the field.

For these functional profiling assays to be extremely effective, they need fresh "live" tumor specimens. There are very good reasons for using fresh "live' tumor specimens and not needle biopsies for cell-based functional profiling assays. The surgical specimen is the "personalized" part of personalized cancer medicine.

In the body, cells interact with and are supported by other living cells, both malignant and non-malignant cells. That is why cell-death functional profiling assays study cancer cells in small clusters, or microspheroids (microclusters).

Analysis of these microspheroids provides a snapshot of cancer's behavior within the human body and provides a more accurate representation of how cancer cells are likely to respond to treatment in the clinic. It will be indicative of what will happen in the human body. There is no manipulation of isolated cancer cells to make them grow.

Real-life cancers grow as a complex organism that includes both malignant and non-malignant components. It may include fibrous tissue, mesothelial cells, fibroblasts, epithelial cells, 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.

Cells are routinely broken up by mechanical and enzymatic means, which 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.

In short, it is a complex and thorough analysis. Not many medical oncologists understand it.

http://cancerfocus.org/forum/showthread.php?t=3473

Joann

Molecular profiling uses DNA sequencing to determine gene mutations in the DNA of a tumor. It is a tumor analysis coupled with clinical literature search, which "tries" to match therapies to patient-specific biomarker information to generate a treatment approach. In other words, information that may help when considering "potential" treatment options (theoretical analysis).

Functional profiling takes the tumor, with the surrounding tissue (intact and live) and then chemo is put on it to see which "actually" kills the cancer cells. It actually measures the response of tumor cells to drug exposure. It measures biological signals rather than DNA indicators. Following exposure, both cell metabolism and cell morphology is measured. The integrated effect of drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome.

Molecular profiling is testing for mutations, functional profiling is testing for drugs. Rating the efficacy of population research on the one hand, while the other is rating the efficacy of drugs "actually" tested against an individual's cancer cells.

Greg