Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Here’s a nice paper that I’ve been reading, written by Tim Harris and Frank McCormick on cancer biology.  Lately, we’ve all seen how advances in DNA sequencing and genome-wide association studies (GWAS) are driving the discovery of the germline and somatic mutations that are present in different cancers.  This article sets out to review:

“The most important molecular changes in different cancers from the perspective of what should be analyzed on a routine basis in the clinic.”

Essentially, this is an overview of where we are in both hematologic and solid tumours and looks at the molecular subsets that are emerging, hopefully as targets for therapeutic intervention.  I’m not going to repeat their excellent article, but if you are really interested in this field, I highly recommend reading it.  A link is provided below after the post to the actual paper.

What struck me most though, was not the nice summary of what we know about the biology of cancer, but their vision of the future in cancer medicine:

“The year is 2020. I wake up and feel the lump under my arm that has been bothering me for several weeks. I decide to make an appointment with the doctor to find the cause, especially since my personal genetic analysis has highlighted alleles that are associated with an increased risk of cancer.

The doctor’s receptionist views my electronic health record online before I am buzzed in to see the doctor.  Once I have explained the problem, a biopsy from the offending lymph-node is taken, the tissue is flash-frozen using the nitrogen quick-freeze system, and then delivered to the laboratory downstairs for a rapid molecular work-up.

DNA from the tissue is sequenced to identify any mutations in the 500 most common genes known to be involved in cancer. Tissue sections are analyzed using high-resolution fluorescent optical images.  A blood sample is also taken to check my background genomic DNA sequence, concentrating on alleles known to predispose to lymphoma.  Sequences for the genes encoding drug-metabolizing enzymes and drug-distribution proteins are also obtained.

A proteomic work-up is undertaken to look at protein profiles and post translational modifications.  I also undergo new-generation imaging so the gross pathology of my organs can be viewed in three-dimensions.  Two hours later, I review the results on my handheld computer device. The results have been predigested and presented as a simple digital read-out so that a diagnosis, prognosis and appropriate treatment can be derived.

Fortunately, the overall molecular and cellular pathology of the lymph-node is considered normal.  Apart from my pre-existing heart disease, all other organs appear to be healthy and I am prescribed an anti-inflammatory drug.

I leave the doctor’s office with a sigh of relief that all appears to be well.”

Whoa, that may sound like something from Bones in Star Trek initially, but I suspect it may well not be as far fetched as we imagine.  Why?   Because over the last two years the progress made in systems biology and cancer genome studies have encouraged me greatly.  What was a fledging area of cancer research is now becoming very much to the forefront of new breakthroughs and increased understanding of what is happening at the molecular level and new prognostic and predictive biomarkers are emerging.

Of course, there is still a long way to go in the war on cancer, but I see plenty of signs that much progress is being made.  Where we may well fall down though, is not in the science per se, but rather in our efforts of communication and coordination:

“The stakeholders, which include the payers, health care organizations, pharmaceutical and biotechnology industry, and molecular diagnostics companies, need to be aligned to achieve the most effective partnership.”

We clearly have much to do in this direction.  We have many of the electronic tools available already and yet speed of testing, diagnosis, access to electronic patient records (EHR) and in particular communication, is often snail mail slow.  How many of us receive test results instantly on our PDAs or email? How many have physicians or other service providers who even communicate with their patients by email or other technologies? This needs to change, and for the better.

There are some nice examples of real empowerment emerging from the cancer community, as this post from my friend Jody, a breast cancer survivor, shows in her recent blog post.  It’s a great start and I hope to hear of many more examples like this.

What do you think?   What can be done to improve the delivery of healthcare for people with cancer and how can we foster greater collaborations?
Harris, T., & McCormick, F. (2010). The molecular pathology of cancer Nature Reviews Clinical Oncology, 7 (5), 251-265 DOI: 10.1038/nrclinonc.2010.41

8 Responses to “The molecular pathology of cancer: a glimpse into the future”

  1. philbaumann

    It’s a very cool glimpse into the future!

    …Although I suspect 2020 might too early 😉 – at least for some aspects of the crystal ball.

    But I do think that we are in reach of making access to information WAY better than today, and even that alone would be a considerable improvement.

    Not to mention: better *access* to communication increases the chance of sharing for research purposes.

    • maverickny

      Thanks for stopping by, Phil.

      I really do hope to see serious improvement before 2020, especially as the technologies for better communication alone are already out there. One of the big challenges though, seems to be sheer inertia in the system that make many feel like a lone Sisyphus pushing the huge rock up the hill.

      The more we share, the more we all learn.

  2. Claudia Donnet

    I loved that the imaginary travel to the future did not stop with the genomic analysis of the flash frozen tissue but continued onto the post-translational modifications (well, I may be biased since I worked for a while on such a project, looking for phosphorylation status of the phosphotyrosine signaling networks in cancer tissues). We could do that in a research lab at MIT. The technical resources are already available!

    • maverickny

      Howdy Claudia,

      Yes they are already available, exactly! Somehow we still struggle with translating bench to bedside though…

      • Claudia Donnet

        Well, I can see one big reason that our phosphorylation analysis cannot be easily translated to bedside or doctor’s office, which is the complexity of the technique. At least, in the way we were doing it for research purposes. It may be difficult to get a quick method, due to the tiny proportion of the phosphotyrosine proteins involved in the process of signal activation. Our method –for discovery– involved about 2 days work, including two fractionation/purification steps and then a long run on a mass spectrometer. This could however be simplified once you define exactly what you’re looking for, perhaps an array methodology with the right sensitivity and specificity for phosphorylated site? I need to explore more in the literature what’s going on in that regard.

  3. Nancy Roach

    NCI and the extramural cancer research community are actually doing quite a bit to reward collaboration and harmonization. – look at the Operational Efficiency Working Group recommendations, which are already cutting down the time it takes to open protocols. At the December Clinical Trials Advisory Committee meeting, a subcommittee will be presenting recommendations on how to increase collaboration.

    • maverickny

      Hi Nancy,

      That’s really good to hear and it’s certainly collaboration initiatives like these that will help make a difference in speeding things up. I’ll keep an eye out for the Dec meeting.

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