New assay test shows positive results for patients with recurrent or metastatic breas

[News]

When breast cancer advances, the patient doesn't have the luxury of time. Finding the right type of chemotherapy as quickly as possible is a critical factor for the patient's success and, until now, predicting the patient's sensitivity to chemotherapy has often been a shot in the dark.

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[gdpawel]

What is missing in the article is that DiaTech is NOT the only one on the market that can tell an oncologist the most effective chemotherapy treatment for the patient.

They have also claimed that they are the only commercial pathology reference laboratory in the U.S. that works exclusively with "live" cancer cells and the only one that has the expertise and technology to measure drug sensitivity of specific cancer cells.

Perhaps they are making this misleading claim because they are licensed as a pathology laboratory, while other laboratories have been pigeonholed as immunology laboratories by the FDA.

DiaTech Oncology uses the MiCK assay which is their "brand name" for a caspases assay (caspase-3-mediated apoptosis). It correlates precisely with the findings in the DISC, MTT and ATP assays.

Following the description of apoptosis in the British Journal of Cancer in 1972, scientists around the world incorporated the concept of programmed cell death into their cancer research. What is less understood is the fact that apoptosis is not synonymous with programmed cell death.

Programmed cell death is a fundamental feature of multicellular organism biology. Mutated cells incapable of performing their normal functions self-destruct in service of the multicellular organism as a whole.

While apoptosis represents an important mechanism of programmed cell death, it is only one of several cell death pathways.

Apoptotic cell death occurs with certain mutational events, DNA damage, oxidative stress and withdrawal of some growth factors particularly within the immune system.

Non-apoptotic programmed cell death includes: programmed necrosis, para-apoptosis, autophagic cell death, nutrient withdrawal, and subtypes associated with mis-folded protein response, and PARP mediated cell death.

While apoptotic cell death follows a recognized cascade of caspase-3- mediated enzymatic events, non-apoptotic cell death occurs in the absence of caspase activation.

With the recognition of programmed cell death as a principal factor in carcinogenesis and cancer response to therapy, there has been a growing belief that the measurement of apoptosis alone will provide the insights needed in cancer biology. This oversimplification underestimates the complexity of cell biology and suggests that cancer cells have but one mechanisms of response to injury.

It has previously been shown that cancer cells that suffer lethal injury and initiate the process of apoptosis can be treated with caspase inhibitors to prevent caspase-3-mediated apoptosis. Of interest, these cells are not rescued from death. Instead, these cells committed to death, undergo a form of non-apoptotic programmed cell death more consistent with necrosis. Thus, commitment to death overrides mechanism of death.

Labs that focus on measurements of caspase activation can "only" measure apoptotic cell death. While apoptotic cell death is of importance in hematologic cancers and some solid tumors, it does not represent the mechanism of cell death in all tumors.

While caspase activation is of interest, comparably easy to measure and useful in many leukemias and lymphomas, it does not represent cancer cell death in all circumstances and can be an unreliable parameter in many solid tumors.

Laboratories that measure only one mechanism of cell death (e.g. caspase activation as a measure of apoptosis) miss important cell responses that are critical to the accurate prediction of clinical response.

Also noted, the use of a (MiCK) caspase-3 activity test for the assessment of ex-vivo chemosensitivity do not correlate with sensitivity or resistance to commonly employed anticancer drugs in AML patients (BMC Cancer 2005, 5:60 doi:10.1186/1471-2407-5-60). Established tests like the DISC assay or the MTT assay are still the best choice for predicting chemosensitivities of cancer cells.

In regards to caspase-3 activity testing for solid tumors such as colorectal carcinoma, bladder carcinoma, neuroblastoma, breast and lung adenocarcinoma, no studies have been published. Clinical studies to establish correlation between the (MiCK) caspase-3 assay results and treatment outcome in patients with solid tumors are still under way.

['lizbeth]

gdpawel,

that is a lot of great information. Can you rephrase this in a simpler way?

I'm asking what the heck you just said, and what you would recommend instead.

[gdpawel]

'lizbeth

I just don't know what to think about DiaTech. A number of years ago I wrote to Gary about why they posted on their website that the DISC and MTT assays (two of a number of "cell-death" assays) were "cell-growth" assays. They are "cell-death" assays, not "cell-growth" assays. They never corrected this misinformation. I let it go. Now I read on this press release that they claim they are the only commercial reference laboratory in the U.S. that works exclusively with "live" cancer cells and the only ones with "expertise and technology" to measure "drug sensitivity" of specific cancer cells. Why the deceptive advertising? They are not the only one in the U.S. I just wanted to point that out that misinformation.

Assays use an endpoint, which is a point of termination (end result). Four "cell-death" assays are DISC, MTT, ATP and Caspase 3/7. The DiaTech MiCK uses only one caspase assay. This is the only endpoint they use. I pointed out that while apoptosis represents an important mechanism of programmed cell death, it is only one of several cell-death pathways. There is apoptotic and non-apoptotic programmed cell-death pathways. Caspase measures only the one type. In order to measure all types of pathways, you need two or more of the "cell-death" endpoints (DISC, MTT, ATP and Caspase). Relying on only one endpoint is not very accurate!

Labs that focus on measurements of caspase activation can only measure apoptotic cell-death. Now that's important in hematologic cancers and lymphomas, but it does not represent the mechanism of cell-death in all solid tumors (like breast cancer). Laboratories that utilize functional cytometric profiling use combined metabolic (cell metabolism) and morphologic (structure) endpoints. A lot more "accurate" in measuring all manner of apoptosis (cell death).

The difference between cell-growth and cell-death assays is that cell-growth assays look to see which drugs inhibited the cancer cells' growth (cell-growth), while cell-death assays look to see which drugs actively kills the tumor cells (cell-death). Cancer doesn't grow faster than other cells, it just dies slower. Cell-death assay technology connects drugs to patients by what "kills" their cells, not by what "slows" them down. And they certainly don't just measure what genes or proteins 'hang' out with the cells. They measure the entire genome.

I hope this gives you some better understanding. Cancer is many things, but "simple" is not one of them. I would look for an assay that is a lot more accurate than just one cell-death endpoint and an assay that is more accurate than one that chases after what a cell 'hangs" with.

Greg