Weeks 183 & 184: and then there was... ALK!

Written by Lars Haakon Soraas

Weeks 183 and 184 in the war on lung cancer have passed. There has been an interesting turn of events. Here are the highlights:

  • A couple of weeks ago, we got the results from some analysis BC Cancer Agency in Canada very kindly did for us. In short, they have a program where they do in-depth analysis of the type of whole exome and RNA sequencing data that we have obtained from the biopsy Dyanne did in October last year. They kindly agreed to analyse Dyanne’s data and the report we got back, which I think is both extremely fascinating and intriguing, can be found here.
  • They made several interesting findings. I will not go through all of them now; perhaps we come back to some of them in the near future. However, one of the most interesting things they found was that Dyanne’s tumor had a very high level of ALK expression. As readers of this blog will know, the mutation Dyanne has struggeled with since diagnosis in 2015 is in the EGFR gene. ALK is, however, another gene that is frequently mutated in never-smoking lung cancer patients. But it is rare that those who have EGFR also have ALK. It has been described in the literature, however. Here is a short paper describing two cases where ALK is a resistance mechanism to EGFR inhibition and here is another paper with one more such case.
  • The good news, or so we hope, is that there are several good drugs that are effective against ALK mutations. Thus, based on the finding from Canada, immunohistochemistry (IHC) testing for ALK was done. And this turned out very positive (i.e. ALK was found). Intriguingly, another test, a so called FISH test, that had been done to detect ALK back in October was negative (i.e. no ALK was found). What to make of ALK being positive on IHC, but negative on FISH? Well, someone has looked into this, and it seems that the most important is to be positive on IHC. In other words: those who are IHC positive, but FISH negative, tend to respond to ALK inhibitors.
  • Based on all this, Dyanne started an ALK inhibitor called crizotinib (Xalkori) on Wednesday last week. Crizotinib will be done in parallell with the EGFR targeting drug she is on, ie. osimertinib. We will, in the coming couple of weeks, track CEA and NSE closely to see if there are any indications that the drug is having the hoped for effect. Time will show.
  • Prior to starting crizotinib, Dyanne stopped simvastatin, doxycycline, fenbendazole, curcumin, vitamin E, disulfiram and mifepristone. The main reason is tolerability and potential interactions with crizotinib.
  • Dyanne has been in ok shape the last couple of weeks.

Hope everyone has had a good weekend!

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