A shortcut to precision cancer treatment

The world is changed. I feel it in the water. I feel it in the earth. I smell it in the air.*

The elves might not be real but their message is more than real – we see the world change before our eyes faster than ever. That change was brought by next wave technological revolution that swept also the world of life science. It took over 10 years at the cost of 3 billion $ to sequence the first human genome. Today, after approximately 3 weeks and 1000$ we can hold in our hands the info of who we are at the level of the genetic code.

But why is that important?

It is the first time when the humanity can realistically think of tailoring cancer treatment to every single patient.

The age of one-fits-all approach is over. The time of the precision medicine has come.*

Precision medicine will allow matching the right medicine with the right patient. Drugs save lives but they also carry risks of side-effects, especially cytotoxic drugs used against cancer. However, there are drugs designed to interact specifically with proteins present only in tumor cells, minimizing those unwanted side effects. But first we have to know if that patient has those potential proteins. Sequencing patient’s tumor lets us find out and allows predicting if that medicine will work for that person or not. So far so good, but …

But cancer is an extremely multifaceted disease.

Sometimes we can find that one, specific, mutated protein that is not only the cause of the problem but also the lifeline for the tumor. We can match the treatment with the target and save that patient’s life. But often, it is very difficult to find that one, clear target. Some tumors have very complex genomes and we are not sure which of the mutations are the primary cause of the disease or which are crucial for tumor’s survival. Or it might happen that that particular tumor doesn’t have a clear target. Does that mean precision medicine has failed?

Where there's life there's hope.*

The research group I am a part of is working with such difficult to target tumors - sarcomas. We are working hard on finding the weak points of sarcomas, collecting information on genomic changes of tumors from multiple Norwegian patients. But what if we didn’t have to find that answer? What if we could bypass the complex interactions happening in the cell and directly test which drugs kill that patient’s tumor cells? We have proposed such a shortcut, a different approach to precision medicine: drug sensitivity/resistance screen for sarcoma patients. How does that work?

The idea is based on so called drug repurposing – using the already known drugs for new indications. For instance, when a drug normally used against breast cancer is used against melanoma. But which drugs to take and how to test them?

We select drugs which are already approved for cancer patients or are in advanced stages of clinical trials. Our Anti-Cancer Compound Library contains around 350 drugs. We get a sample of patient’s tumor, isolate cells from it and mix them with the drugs from the Library.  After 3 days incubation we check which cells are killed. At this stage we know, which drugs could potentially work for that particular patient. So should a patient be given such drug?

Human body is a complex system, so we cannot be certain that those drugs will work equally well if administered to the patient. But we are almost certain that those which did not kill the tumor cells outside the body, will not be helpful. Anti-cancer drugs do have heavy side-effects and it is critical if we can eliminate those which would not have any effect for that particular patient. We need to gather enough evidence to be sure that the results of our drug sensitivity/resistance screen reflects what happens in patients, therefore we are now collecting data on how our sarcoma patients are responding to chemotherapeutics (which are a part of our library as well). It will take time and effort but hopefully we will be able to bring precision medicine also to those complex cases where genomics-based personalized therapy could not yet offer a solution.

 

* yes, I am a big fan of “The Lord of the Rings” :-)

By Iwona Grad
Published Oct. 17, 2018 12:57 PM - Last modified Oct. 17, 2018 12:57 PM
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