Monday, 5 January 2009

The Increasing Use of Biomarkers in Cancer Research

Hello and welcome to my first 'SciBite'. Whilst looking for a subject to write my first post about I came across an article about prostate cancer and a particular type of androgen (male hormone) receptor. This article details the discovery of several variants of androgen receptor, and how the expression of one particular variant seems to be responsible for enabling prostate cells to grow even without the androgens they usually require.

This is important because current standard treatment for prostate cancer often involves disrupting this androgen signal, either by castration, or more commonly in the richer countries of the world, hormone therapy. Both of these methods are initially highly successful, often large decreases in the size of the tumor are observed, but frequently the cancer develops independence from the androgens that used to dictate its growth, and a new phase of the disease is entered.

The discovery of this variant androgen receptor sheds some light on the mechanism of the cancers evolution to this phase, but usefully it also provides a 'biomarker' to help consultants decide the best course of therapy to place their patient on. It is possible to test a biopsy of the tumor to establish if this variant receptor is present, if it is already present at a high level then hormone therapy may not be a very successful option and the patient may benefit from an alternative treatment. For patients who are undergoing hormone therapy, it may provide a useful guide as to how far along the tumor has got to becoming androgen independent, and enable a switch to another treatment before tumor growth becomes completely uncontrolled.

This is one good example of a current trend in cancer research and treatment: Identification and utilisation of biomarkers to better diagnose, monitor and treat cancer. Previously cancers have been categorised according to the organ or tissue of origin, and all cancers of that origin tended to be treated the same way. However, more recently new technologies such as gene expression profiling have shown that the genetics of tumors can differ greatly between patients, even if the tumors are in the same tissue. Furthermore it has exposed the fact that there can be large genetic differences even within a patients own cancer, primary tumors being significantly different to secondary tumors. The differences extend beyond the genomic level, as all changes at that level are translated into cellular changes, the up or downregulation of tumor specific proteins may be detectable in the blood as is the case with PSA in prostate cancer.

These differences go some way to explaining why cancer treatment has until now been so hit-and-miss. If cancers of the same tissue can be caused by completely different mechanisms, then it is unreasonable to expect one treatment to be successful with them all.

The advantage we gain from the genetic analyses available to us now is that we can see easily which genes are undergoing changes in the development of a cancer, and investigate them specifically. This will inevitably provide many new cancer biomarkers to help us understand the processes occurring within cancers, give us a clue about the prognosis for the patient and enable us to more precisely target specific processes in the tumor with proven drug combinations.

I recently heard a speaker at a lecture say something along these lines: "We don't need to develop any new cancer drugs, we already have a lot of those, we just don't fully understand how they work or who they will work for, and that is where we need to focus our efforts".

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