Patient-Derived Xenografts

In my last post, I mentioned that I’ve been asked to take part in an interesting study to help develop a new form of cancer therapy. That therapy is based on Patient-Derived Xenografts (PDX). It works roughly like this:

  1. They extract a sample of your tumour, and divide it into two bits.
  2. They take one half, and implant it under the skin of an immune-deficient (“nude”) mouse. The immune deficiency means the mouse does not reject the graft.
  3. If it grows in the mouse, once it’s large enough they remove it and implant it into a second “generation” of four mice.
  4. They keep going for four generations, so at the end you have about 64 mice. It turns out that if you can get a tumour to grow for this long, it is acclimatised to the mice and will grow forever if required.
  5. Next, they take the other half of the sample and do a deep genetic sequence on it, along with one of a normal bit of me.
  6. They “diff” the two sequences to find all of the mutations that my cancer carries.
  7. Some of those mutations will be “driver” mutations, responsible for the cancer being cancerous, and others will be “passenger” mutations, which happened at the same time or subsequently, but are just along for the ride. They try and work out which are which.
  8. If they can identify the driver mutations, they look and see if they have a treatment for cancers driven by that set of mutations.
  9. If they do, they feed it to the mice.
  10. If it works in the mice, they give it to me.

As you can imagine, there’s a lot that can go wrong in this process. The biopsy samples could be bad, the tumour may not grow in the mice, or it may not grow for long enough, they may not be able to figure out which mutations are drivers, if they can there may not be an agent targetting that pathway, if there is it might not work in the mice, and if it does it might not work in me! So it would be wrong to trust in this for a “cure”. As before, my life is in the Lord’s hands, and he alone numbers my days. But I hope that even if it does not result in a cure for me, the knowledge gained will help them to cure others in the future.

I have significant involvement only at the beginning and (if we get there) the end. To start the process, it was necessary to provide a tumour sample via biopsy. That happened in London yesterday, and the rather eventful experience will be the subject of my next post.

5 thoughts on “Patient-Derived Xenografts

  1. So, presumably, each of your cancer occurrences might have different mutations. So treating each of them is like treating a different one in a different person, even with that experimental treatment. I guess we’re not quite there for _the_ cancer cure. Pretty amazing where we are, though.

  2. It’s possible. My cancer is quite slow-growing, so the chances of it picking up additional passenger mutations along the way are less than they would be for a rapidly-dividing cancer. But then, I’ve had it for a lot longer. So maybe that balances out.

    It is indeed possible that different bits of my cancer have different mutations – but that could actually be a benefit. If they sampled two different lumps, only the mutations common to both would be candidates for being driver mutations.

    Hmm… If only they’d stored the samples from my initial operations in 2001, perhaps they would be better candidates for sequencing, because they would have had less time to pick up passengers. It seems to me that if you get cancer today, the first thing you should do when they remove any is insist that some of it is preserved and frozen in a way which preserves the DNA.

  3. Pingback: PDX Biopsy | Hacking for Christ

  4. Hi Gerv,

    I don’t know if you have been made thoughts yet about the natural way in beaten the cancer. Chemotherapy and any other medical surgery have a lot of bad side-effects, up to bringing your whole immune system down. Then it is even harder for the body to fight against the remaining bad cells. I think you really should check those studies. If you are interested in more facts, I would happily send you more information. Most is in German, so I may have to find English material first. But for now, people got rid of cancer by forcing themselves to eat healthier food (no carbs, more protein), doing more sports (best is running), and finding time to refresh their body. Whatever you choose, I wish you all best!

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