New Findings and Potential New Drug for Squamous Patients - 1247896

Thank you for posting this, Laya. It would be great to hear from a doctor on this topic, perhaps when the Nature paper has appeared and there has been time to digest it.
There is obviously quite a bit of work going on in this area. At the time of the ASCO conference Dr West mentioned a study by MSK in New York, also looking at mutations in squamous tumours:
cancergrace.org/lung/2012/05/19/my-top-5-notable-asco-2012-abstracts-in-metastatic-nsclc/#more-10537.
I agree that it's great to see this research is happening. But Dr West made the point that there aren't yet the drugs to match the mutations, so that slightly tempers my enthusiasm. Also everything I've read - and Dr William Pao confirms this in the NYT article - suggests that squamous tumours are more complex and less likely to have a single "driver" mutation.
I couldn't work out from the NYT report of the Nature paper what specific drug they were talking about (there was a reference to a new immunotherapy drug that was unexpectedly found to work on a sub-category of squamous tumours - only 3 per cent - that that somehow evade the immune system).

I need to review it more carefully. I'm not seeing anything at first glance that would justify the media acting like it's unfathomably novel compared with some of the same work that we've been talking about for years that different cancers have very specific molecular profiles (and we''ve even seen this in regard to squamous cancers). I don't think there's a real answer to the question of how this will change lung cancer treatment in the next 3-5 years.

-Dr. West

I have been trying to get to grips with this, and was struck by a quote from Dr Govindan, who was involved in the recent GRACE webinar on immunotherapies. He is part of The Cancer Genome Atlas (TCGA) team behind the Nature paper that is generating these reports.
Dr Govindan said of the TCGA study, which looked at squamous tumours from 178 patients: "We found that almost 75 percent of the patients' cancers have mutations that can be targeted with existing drugs — drugs that are available commercially or for clinical trials,"
(I am getting this from http://www.genomeweb.com/sequencing/tcga-team-reports-squamous-cell-lun…. The same statement is contained in an ASCO abstract of the work on mutations in squamous tumors, # 7006 from 2012.
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&…
The Nature paper is available at http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11404.html.

As to the "potential new drug", a more detailed report in Science Daily was useful in trying to work out what this is all about:
http://www.sciencedaily.com/releases/2012/09/120909150439.htm
The gene that seems to help a small percentage of squamous tumours "evade" the immune system is HLA-A (mentioned in Dr Brahmer's immunotherapies presentation). There are Phase 1 trials going on in Japan for a "peptide cancer vaccine" that targets HLA-A , so I am guessing that this is the "potential new drug".

One interesting (for me) incidental finding is that the researchers found the incidence of EGFR mutations to be 1 per cent (out of 178 patients with squamous tumours).
Dr Matthew Meyerson, who is involved with the Cancer Genome Atlas project, says: "In squamous cell lung cancer, it was actually thought that [EGFR] wasn't a good target .... but they [EGFR mutations] are there and that should actually give us a target to hit in the future".
(Source: interview with Dr Myerson at http://benchmarks.cancer.gov/2012/09/matthew-meyerson-discusses-tcga-lu…)

I agree that we always knew that EGFR mutations as well as ALK rearrangements are very uncommon but not impossible in patients with squamous tumors. One real advantage once we reach a point where lung tumors are routinely interrogated for a battery of molecular markers is that it will reach a level of efficiency and scale where it's possible to identify the rare but very actionable molecular target in populations in whom it's far less feasible to do mass screening for a rare target now.

-Dr. West

What I'd still like to understand is how the researchers arrived at the figure of 75 % of squamous patients (out of the 178 in the research study) who have mutations that could potentially targeted by drugs now in clinical trials - and what the trial drugs are:
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&…
It would be great to have someone with a knowledge of molecular pathology and time on their hands cast an eye over that part of the Nature paper entitled "Therapeutic targets", so as to explain it to non-scientists:
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11404.html
Or perhaps we could ask Dr Govindan back to give us some insight?
For me, it doesn't actually matter if this research will take years before it comes to fruition. Just to know it is out there is encouraging, even if I will be long dead by then.

I'll see about reaching out to Dr. Quesnelle or perhaps Dr. Govindan...I agree that the numbers are a little charitable -- they tend to include situations for which there are agents somewhere on the planet with even putative activity against an identified target, which is a far cry from these treatments being demonstrated to be both beneficial and tolerable.

-Dr. West

Thank you, Dr West.