Biomarkers

This is an excellent question. Caris is a member of a group of molecular profiling companies. These groups extract protein, DNA or RNA and measure the genetic information present in fixed tissue. Their intent is to match patients to therapy based on this static data. That is, the presence of a gene should, according to their reasoning, confer sensitivity to a drug. The proof of this concept, however, is sorely lacking. If we examine one publication in the literature (VonHoff D et al, J Clin Oncol Nov 2010), we find an objective response rate (measurable benefit in 66 patients treated using molecularly selected drugs) of 10%. Indeed, the positive results reported in this study reflected not a response rate but instead a 30% improvement in the time to disease progression, associated with molecular drug selection, compared with the patients prior, most recent (unsuccessful) therapies. To put this in context, a patient could arguably fail a physician-selected treatment after 1 month, and then receive a Caris selected therapy. If they responded for 1 month plus 10 days (a 30% improvement), they were counted as a success. The clinical relevance of that degree of improvement seems questionable.
While we fully understand the excitement surrounding genetic analyses, the more sophisticated researchers in the field are beginning to appreciate that the complexity of human biology demands more global (functional) analytic platforms that encompass all of the mechanisms of response and resistance. In this light, the presence of a gene cannot predict whether that gene will be expressed, active, counter-acted by a complementary gene, or functional.
We believe that human biology must be taken at face value in its most complex state. This is known as the phenotype and must be examined for the biological features that these interconnected cellular systems create. This field now known as biosystematics, or systems biology, recognizes the redundancies and uncertainties that separate the genotype (molecular profiling) from the phenotype (functional analyses) are not trivial. Our laboratory conducts phenotype analyses. Caris conducts genotype analyses.

There are numerous additional biomarkers under investigation. It is important to note that different biomarkers are likely to be useful for different reasons. Some biomarkers may help predict or determine responses to particular treatments and others may be useful in predicting how aggressive a particular cancer may be. Still other biomarkers are being tested as new diagnostic tools, for early detection of breast cancer.

Biomarkers can be found in the tumors themselves or in blood, urine, feces or even in breath samples.
They can be made of protein, RNA, or smaller biochemicals. Some biomarkers are actually measures of larger 'states' of the cell, including the stability of the chromosomes. There are too many under investigation to list them all here, but they include: Ki67 (a protein marker of cell division), chromosome length, and some microRNAs. For more details, see http://www.ncbi.nlm.nih.gov/pubmed?term=breast%20cancer%20biomarkers .

A biomarker is something that provides information (often indirectly) about a biological process or event. An example is elevated cholesterol. High cholesterol is frequently associated with coronary heart disease and so is a biomarker for heart disease.

With respect to cancer, there are different types of biomarkers that are used to guide treatment. In breast cancer, there are several that are routinely checked by pathologists.

An example using the estrogen receptor (ER): The estrogen receptor is a protein the binds to estrogen (when it is present). Once they are bound together, the receptor:estrogen duo can cause the activation/repression of a variety of genes, altering cellular activity. In general, estrogen acts as a growth factor for breast cells. When breast cancer is diagnosed, the cancer is examined for the presence of the the estrogen receptor. If it is present, that is an indication that the cancer cells are still 'listening' to the signals sent via estrogen. If the ER is NOT there (but the cells are still dividing - causing the cancer), it is an indication that the cells are more abnormal. They no longer require the signals provided by estrogen.

What does this mean for the patient?
Breast cancers that express the estrogen receptor (ER positive) may respond to treatments that block estrogen production/activity (i.e. tamoxifen).
ER negative tumors may be more aggressive and are not nearly as likely to respond to ER blockers (antagonists).

Other biomarkers in breast cancer include the HER2 protein (a growth factor receptor) and the progesterone receptor (PR).

The identification of biomarkers allows clinicians to personalize the treatment of individual patients, based on their molecular profiles.

Widespread use is something that will not happen easily in any research related to cancer. Sorry.

Most of the advancement in cancer research is an increment. Step by step. Further, IBC is under funded so it makes the situation more difficult.

MD Anderson Cancer Center focuses now on targeting EGFR, HDAC, VEGFR, c-Met, HER2, IGFR and etc. There are many targeted therapy trials conducted specially targeting IBC or including IBC.

I am guessing that you are asking how you develop a novel biomarkers or a new targeted therapy for breast cancer or inflammatory breast cancer.


There are several ways to approach this issues.

1. You collect large amoung of tissue and blood samples from breast cancer. Then you do a comprehensive analysis of genetic and protein changes (DNA, RNA, and protein). You link this data to a clinica data and find the one or them that can impact surveil or disease recurrence.

2. The other approach is discovery from basic research needs to be mined. And take their knowledge to apply by conducting a hypothesis oriented research. This means that you build up the puzzle one by one to prove the target is truly relevant in breast cancer.

Both approaches are important. Therefore, we do both and spend tremendous amount of time an money to come out with a strong scientific rationale before we can test this in human being. The problem we face is that there is not enough money and those who qualified to do this type of research.

Please asks me a more specific question. This may help me to answer this more accurately.