This week, a couple of new studies (which can be found here and here) showed that we can track changes in a tumour through blood samples alone. To understand the importance of this it is worth knowing that chemotherapy is going through a radical change at the moment.
The last few years have seen the introduction of a new generation of cancer drugs. These are targeted therapies, ones that are targeted not only towards a specific cancer but also towards specific sub-types of that cancer, based on the mutations that they have in their DNA. Not only are these chemotherapies more effective, but they should also cause fewer side effects than ones used in the past. Several of these targeted therapies have proven to give remarkable responses, with tumours melting away better than we could have dreamed.
However, as patients have taken these drugs, an unfortunate pattern has emerged: the patients show amazing responses for a few months, but pretty quickly resistance emerges and the tumours regrow, now insensitive to the therapy.
In fact, the very specificity of these drugs is actually their Achilles heel. Because they are designed to target a specific mutation in a specific gene, if certain other mutations occur in the same gene, they can result in resistance to the therapy (for an example of this, see below).
It is in this background that the studies mentioned above could prove very important. These studies showed that simply by looking at the blood of patients, the scientists could track what mutations were happening in the tumour. This is because cancers shed lots of DNA into the blood stream, and the researchers could detect and analyse this. They showed that they could track the tumour as it developed, looking at what new mutations were arising. In effect, they could predict resistance to a drug before it became apparent in the patient. Not only that, but they could see how the resistance was happening and suggest alternative therapies that may be effective.
This is all very good news. Previously, the only way of doing this was to take a biopsy of the tumour itself, a very invasive procedure that carries its own risks, and one that cannot be carried out regularly. With this new method, we will hopefully be able to monitor the tumour much more closely (patients shouldn’t object to giving blood every couple of weeks), and be proactive in treatment, rather than reactive.
This method is still too expensive to be made commonly available, but the cost is rapidly decreasing, and it should be accessible in the near future. Additionally, with the move in cancer treatment towards targeted therapy, this will hopefully majorly increase the effectiveness of our new generation of therapies.
Example of resistance to a targeted therapy
A drug designed for some lung cancers was targeted towards a specific mutation in a pro-growth protein called EGFR. In these cancers, EGFR was stuck in the “on” position as a result of the mutation, which meant it was driving uncontrolled growth. The drug was specifically developed to turn this protein off again, which resulted in it hitting the cancer, and largely leaving other cells unaffected. This therapy worked beautifully in patients for 10 – 14 months, but resistance appeared after that and we were back to square one in our options for treatment. When they looked at the new, resistant tumour, scientists found that the resistant cells had picked up additional mutations in EGFR, activating it in a different way. As a result, the cells were resistant to our targeted therapy.