Magic Bullet for Melanoma and How scientist overcome drug resistance

http://sciencefriday.com/segment/07/13/2012/tumors-evade-treatment-with-help-from-neighboring-cells.html

http://cenblog.org/the-haystack/2012/06/asco12-data-digest-overcoming-resistance-in-metastatic-melanoma/

Very good blog talking about the same story:

Not long ago, metastatic melanoma was considered a graveyard for clinical research. But last year brought a major breakthrough in treating skin cancer: the approval of Roche's Zelboraf (vemurafenib), a small molecule that has proven highly effective at treating the roughly 50% of the patient population that carry the BRAFV600E mutation.

However, Zelboraf has limitations. Patients' disease eventually becomes resistant to the drug and the lesions caused by the skin cancer tend to return after 6 to 9 months.

In the backstory, it's the full genome sequencing that has become cheaper to $4000 that will help development of both targetted drugs like anti-BRAF and understanding drug resistance further.   I think the Broad institute is a customer of Complete Genomics.   I have no financial interest btw.   

More quotes:

An amazing thing about current melanoma research is that several physician-scientists involved in the clinical trials are also actively involved in translational research-this is sadly the exception rather than the rule, in oncology. But the connection between basic science and bedside has meant new targets are being identified and quickly tested in the clinic. 

How they pulled off this trick on melanoma is what is important.   Cancer is smart, but people are smarter.

An impressive waterfall plot of tumor shrinkage for patients (n=77) with the BRAFV600K mutation drew gasps from the audience - only four patients failed to respond to the combination, while the majority had a response of 30% or better. This isn't something you see every day in cancer research! Unlike the short lived responses we have seen with single agent therapy, the median duration of response for the BRAF naive patients with the combination was 11.3 months. Treatment given for a median of 10.7 months and just over a third (38%) were still ongoing. With regards to efficacy, PFS was 7.4 months across all dose cohorts, which is slightly above what one might expect for single agent therapy at full dose. 
 ...
He highlighted several key mutations that are druggable – aside from BRAFV600E and K, there is also c-KIT, Q61NRAS, NRAS wt and BRAF wt, where wt stands for wild type. Inevitably, the survival rates for these subsets varies, with NRAS mutants having the worse prognosis.