View Single Post
Old 02-25-2012, 07:35 AM   #29
gdpawel
Senior Member
 
gdpawel's Avatar
 
Join Date: Aug 2006
Location: Pennsylvania
Posts: 1,080
Chemo sensitivity testing

Michka

It's going to depend on the understanding your onc has of a chemo sensitivity test. There are DNA/RNA-type tests based on "population" research (not individuals), virtually the same as it is with tradiational trial-and-error treatment protocol. They base their predictions on the fact that a higher percentage of people with similar genetic profiles or specific mutations may "tend" to respond better to certain drugs. This is not really personalized medicine, but a refinement of statistical data. If you are okay with that, go for it!

Then there is cell-based functional profiling, which provides a window on the complexity of cellular biology in real-time, gauging tumor cell response to chemotherapies (conventional and targeted drugs). By examining drug induced cell death, functional analyses measure the cumulative result of all of a cell's mechanisms of resistance and response acting in concert. Functional profiling approximates the cancer of the "individual" not populations.

The labs vary considerably with regard to technologies, approach to testing, what they try to achieve with the testing, and cost. Some labs have been offering these assays as a non-investigational, paid service to cancer patients, in a situation where up to 30 different drugs and combinations are tested, at two drug concentrations in three different assay systems. The larger the specimen, the more drug types there are in the selective arsenal (minimum 1gm).

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, which was an important point of distinction with earlier cell-growth assays.

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.

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. Don't know if your onc does. Perhaps though, he/she does! The fact the he/she would like to do a chemo sensitivity test and not loose more valuable time and weaken you with ineffective chemotherapy, is a good sign.

Don't know whether he/she intends to ship a specimen stateside or use one of the European labs. All of the labs are experienced and capable of providing very useful information.

Greg
gdpawel is offline   Reply With Quote