:)

- TWR

We actually have amazing targeted therapies (think vemurafenib for V600E mutated melanoma or crizotinib for EML-ALK4 fused lung cancer) but they’re unfortunately not curing (m)any people. Block pathway X (driver mutation) and pathway Y (passenger mutation?) emerges and your magic drug (which goes for $10K/month BTW) is less effective than an aspirin.

 Detecting the mutations following sequencing is not “trivial”. It is an active area of research. There is currently very little agreement between the five or so mutation callers that are in development. It’s a very, very hard problem.

I would tend to agree with bigfatlamer.  An under appreciated aspect of tumor genetics that has been recently discovered that I mentioned in another comment is the genetic heterogeneity.  The mutation rate in tumors is so high that there is never just a single mutation that we can easily screen for and target; at best, we can detect all the mutations and attempt to whittle that list down to the potentially harmful ones which regulate mitosis, for example.  Detecting the mutations following sequencing is trivial, selecting for the harmful ones is much less so, and doing so correctly is extremely difficult.

In an ideal scenario with early tumor detection, there may be a single harmful mutation that we can target.  But, more likely is an array of harmful mutations, and even knocking out the most damaging leaves an intact field of blood vessels that are ready to supply the next most harmful mutation with nutrients.  That is why part of the reason remission is so common, and how tumors gain resistance to chemotherapeutics like bacterial colonies do to antibiotics.

Early detection is, and will always be, on of the most important factors.

I am not sure I agree with bigfatlamer that “they’d publish another 48 stories where a specific, targetable mutation was found and the patient received the targeted therapy and it did F*** all and 6 months later the patient was dead” because if the targetable mutation is found and we have the therapy then the cure rate should be non-negligible.  But certainly I would agree another 48 (or 480) stories should be published where the mutation was not found or the mutation is not targetable.

Currently clinical trials focus on populations of a certain cancer, but not a certain mutation.  To target mutations with clinical trials would require vast and widespread sequencing of every potential enrollee, with +95% discarded for lacking the desired mutation.  Thus, the clinical trial model is a blockage for personalized medicine.

The alternative proposition that was popularized by Andrew Grove (where safety, not efficacy is measured) would allow experimental cancer drugs through, which could then be administered as last resort to patients with the targeted mutation.  This makes a lot of sense for cancer, but could be disastrous for nearly every other disease.—What those “scientists” (ugh) at Duke did was so reprehensible, it is mind boggling.

Was it her will power or the actual medical procedures? Little of both perhaps. 

My best friend died of Hogkins, I still miss him 16 years later. He gave up.

Never give up.

Little-known fact: in addition to the transporter, Leonard McCoy avoided time travel whenever possible.

A more complicated but much more accurate analogy, imagine a beach scene of perfect Waldo impersonators (each representing a genetic mutation), at least one of which has a gun in his pocket and severe mental illness (the active, problematic mutation).  Many others have knives and guns (also harmful mutations).  Even if we use an advanced metal detector, we will have difficulty separating the innocuous Waldo’s from the harmful ones.  We’re currently working on making our advanced metal detector smarter and our profiling more accurate using computational analysis and whole genome sequencing, but there could be 10 psychotic gun wielding Waldo’s and you will be damn lucky if you can identify all of them.

And regarding Big Medicine, there are always some bad apples among any group of people, but we scientists who are busting our asses trying to help take offense to the widespread, blind cynicism that we frequently face (note: I work for a cancer center and not pharma).

it is more like finding the correct waldo in a beach scene filled with perfect waldo impersonators.

I’m not following you there.  If you can find the correct Waldo, they aren’t perfect impersonators.

“Big Medicine” is helping to do their part, they aren’t evil and trying to steal your money.

Some are, some aren’t.  It’s not really that black and white, is it?

no lab would ever accept that info, and would insist on doing (and charging for) their own sequencing.

Maybe the Kickstarter needs to fund a lab too then?  Or maybe some will do it for the positive exposure and/or charity?

I work at an institution where nearly every rare (6 months) response to treatment.

I don’t mean to downplay the importance of the work done by the group at WashU, or the importance of any individual life. I only mean to temper the “OMFG…why can’t we all have all our tumors sequenced right now…are you trying to kill me?!?!” with a little reality.

2011 - Heterogeneity of genetic mutations among breast cancer -
http://www.nature.com/news/2011/110402/full/news.2011.203.html

2012 - Heterogeneity of genetic mutations within a single tumor -
http://www.bloomberg.com/news/2012-03-07/cancer-scans-may-give-false-picture-of-genes-driving-disease-study-finds.html

While it is easy to take a pessimistic look after reading the second article, I am greatly inspired by just how quickly our understanding of cancer is progressing, even now.  There is so much more to learn, and every little bit improves treatment across the board.