bedris

I like how Nassim Taleb put it: "the incentive system put in place by financial companies has produced the worst possible economic system mankind can imagine: capitalism for the profits and socialism for the losses."

For therapeutic index, you want to identify and target antigens that show the largest difference between cancerous tissues and normal tissues (i.e., antigens with a large therapeutic index). In other words, you'd want your drug to bind to an antigen that's present at a higher level on the prostate cancer cells than the normal prostate cells, such that the normal cells are spared.

For antigen stability, you ideally want your drug to target an antigen whose expression is maintained in metastatic lesions. In other words, if a cancer metastasizes from a primary site to a distant organ, and the antigen your drug targets is maintained on the cancerous cells that have made their way to the distant site, then that is a more therapeutically amenable target then one whose expression is lost upon tumor metastasis.

Do those explanations answer your questions well? Let me know if you'd like me to clarify more.

The idea behind these conjugated drugs is that the peptide portion of the drug hones in on a specific biological target and the conjugated cytotoxic drug then kills the cells that have been recognized by the peptide (think warhead and payload). In this case, the peptide recognized prostate-specific membrane antigen, which is expressed on prostate cancer cells, and the cytotoxic drug was one derived from Thapsia garganica, the toxic weed (cytotoxic drugs being isolated from plants is nothing new, of course).

A more common class of these conjugated therapies are called antibody-drug conjugates[1], where an antibody molecule (instead of a peptide) is linked to a cytotoxic drug. There is currently one of these drugs, Brentuximab vedotin, FDA-approved for the treatment of cancer[2]. There are many more under preclinical or clinical development.

[1] http://en.wikipedia.org/wiki/Antibody-drug_conjugate [2] http://en.wikipedia.org/wiki/Brentuximab_vedotin

In other words, this was a $100,000 diagnostic test with no guarantee that an actionable diagnosis would result. By that, I mean that the results of the sequencing analysis either (a) might not pinpoint a driver mutation or (b) might pinpoint a driver mutation that does not have an efficacious drug available to act on that mutation. Also, all caveats about tumor heterogeneity and evolution, etc., apply.

An integrating sequencing approach involving the analysis of normal and cancerous cells to identify actionable mutations is the best we have for now, but it is still a hugely expensive, time-consuming, and technically-challenging process with an enormous failure rate associated with it. Nonetheless, I think it's terrific that, in this instance, it yielded valuable and actionable information that resulted in a meaningful clinical result. One step at a time!

"Supertemps are top managers and professionals—from lawyers to CFOs to consultants—who’ve been trained at top schools and companies and choose to pursue project-based careers independent of any major firm."

It is pretty interesting to see freelancing become a "first-class citizen" in the high-skilled employment world, whereas previously it wasn't widely accepted beyond a few select occupations.

URL: http://hbr.org/2012/05/the-rise-of-the-supertemp/ar/1

This is actually not true. PhD students have to advance to candidacy, which requires completing a set amount of coursework and passing a qualifying exam; this usually takes 1-2 years. Therefore, most first-year PhD students are not yet PhD candidates.

I agree with this. I came across the following definition of an entrepreneur, which I also really liked: "[the] definition of an entrepreneur is someone who makes things happen despite not controlling the resources necessary to achieve them."

Source: http://www.tcpinnovations.com/drugbaron/?p=242

True, but it was sometimes the only way you could do a hard reboot on those things!