Genomics and cancer

Should you know your genetic mutation before starting chemo?

Some medical research has focused a great deal on developing DNA (genomic) tests to identify gene expressions, amplifications and mutations relevant to cancer. The hope is that genetic information will enable researchers to better predict how you will respond to various treatment options.

However, some cancer patients would want to kill their cancer cells, not something that hangs with them. Sequencing the genome of cancer cells (mutation testing) is explicitly based upon the assumption that the pathways of tumor cells (mutations) can be known in sufficient detail to control cancer.

There is this assumption that mutated genes somehow either cause cancer directly or inactivate genes thought to guard against cancer, the so-called oncogenes and tumor suppressor genes. To be effective, a chemotherapy treatment may have to target more than one oncogene: combination chemotherapy.

The more mutations, the further along the tumor may be in its development to malignancy or metastasis. To lay the foundation for personalized cancer treatment using DNA sequencing, the ultimate "driver" is phenotype analysis.

No good gardener would attempt to tell you how your future bouquet will look by simply examining a packet of flower seeds. Similarly, no good doctor should attempt to choose drugs based solely on genotype analysis.

The particular sequence of DNA that an organism possesses (genotype) does not determine what bodily or behavioral form (phenotype) the organism will finally display. 

Good post cp!

I've been following the epigenetic factors in cancer for the last six years. Because of their role in determining the functions and traits of a living organism, scientists have been researching genes in cell organisms to try and find out what they do.

Epigenetic differences explain why two cloned organisms are not the same or why twins develop illnesses of distinct genetic origin. Epigenetics not only adds to our understanding of the relations between the environment and genetics but also provides an explanation of the basic aspects of cell biology.

The knowledge gained can improve the understanding of the development of tumors and can lead to the design of new treatments. A new family of epigenetic drugs are now being used to treat some types of leukemia and breast cancer.

http://cancerfocus.org/forum/showthread.php?t=455

Schoolmom

To date, Oncotype DX (a 21-gene profile assay) is the most commonly used gene expression profiling in clinical practice in the United States. It produces a numerical recurrence score, which places patients in three categories: high risk, intermediate risk, and low risk for recurrence.

The MammaPrint on the other hand (a 70-gene profile microarray assay), is used more frequently in Europe. It reports results via two categories: high risk or low risk for recurrence. I personally feel that MammaPrint is more cost-effective and clinically useful test than Oncotype DX.

But I really like the concept of these tests. They help to predict which women will have a greater chance of breast cancer recurrence. Until these tests, it had been difficult to pinpoint which women would benefit most from chemotherapy and those which wouldn't.

These genotype tests have enormous implications for the short-term future of cancer research in general, and is one of the truly great cancer breakthoughs of our time. They enable the oncologist to more accurately determine who should be treated and who should not be treated with chemotherapy, BUT they cannot predict chemo response!

They will prove to be highly complementary to the parallel breakthrough efforts in targeted therapy through functional phenotype analysis. In real personalized cancer medicine, diagnostics trumps pharmaceutics.

At this point, all they will be able to do is tell you whether you really need to have chemo or not. There is not much else you can do to (again, at this point) to find the most effective (active) chemotherapy (conventional or targeted) other than trial-and-error through the old average population studies.

The phenotype platform has the capacity to measure genetic and epigenetic events as a functional, real-time adjunct to static genotype platforms. The "key" to understanding the genome is understanding how cells work. The ultimate "driver" is functional profiling. The cell-based functional profiling platform has the capacity to measure genetic and epigenetic events as a functional, real-time adjunct to static genomic and proteomic platforms.

Greg

Schoolmom

At this point, there is no good "actual" (phenotype) analysis that can be done, just "theoretical" (genotype) analysis, tumor analysis coupled with clinical trial 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).

You would have needed fresh "live" tumor tissue to "actually" measure the response of your individual tumor cells to drug exposure. Following this exposure, it measures both cell metabolism and cell morphology, the integrated effect of drugs on the whole cell (not something that "hangs with it"), resulting in a cellular response to the drug(s), measuring the interaction of the entire genome.

Perhaps, if or when you recur, you can look into to this in the future. BTW. Aetna does seem quite abhorrent.

Greg

Epignetics likely happens first , turning on or off the wrong genes, this could be related to toxins or

the microenviroment, then after this damage is done the cells split abnormally causing

actual genetic rearrangements, deletions , extra copies of genes etc, causing abnormal

proteins or too many protiens to be made etc, and then the same epigentics make these

abnormal cancerous cells even more damaged, thus the whole thing causes a vicous

cycle as more a more damage is created in each new generation of cells .

This is why they are developing drugs to control epigenitcs

In the late 1990 s experts said HIV would be very hard to cure because the virus mutates

, evolves to rapidly , thats the same reason were given for why cancer will be hard to cure

it mutates, evolves to rapidly

Yet they are now able to control HIV, turn it into a chronic disease,  hopefully the same will happen for Cancer