Friday Grand Rounds: Russ Altman Introduces Pharmacogenomics Database PharmGKB

Every human cell, with two sets of 23 chromosomes, contains six-billion basepairs of DNA (or three-billion per haploid genome).  Of these three-billion genomic basepairs, each individual shares 99.7% with the rest of the humanity.  It is the three-tenths of a percent that determines the differences between all of us.  This tiny percent, nevertheless, comprises of about a million positions that not only make us unique individuals, but also determine how we respond to environment, succumb to certain diseases, or respond (or not) to certain drugs.  These single nucleotide changes, scattered all over the genome, are called single-nucleotide polymorphism (SNP, pronounced snip) - for example, I may have Adenine at position X, you may have C and my friend may have G at the same position.  Since the complete sequencing of human genome in 2003, the post-genomic goal has been, to answer how this 0.3% of genome determines phenotype.  Pharmacogenomics/Pharmacogenetics (PGx) is the study of how genetic makeup correlates to responses to various drugs.  

The Prostate Cancer: New drugs in the post “Abiraterone-Jevtana-Provenge” world

The success of three new drugs (Abiraterone, Jevtana and Provenge) for castration-resistant prostate cancer (CRPC) this year, each targeting different pathways, and all showing an overall survival benefit, has raised the bar for those dreaming to join the club.  There is at least one riding the popularity vote, MDV3100, which may complete phase 3 next year.  Still, many struggle and plough through phase  1 and 2.  One way to understand, what may make some of them unique – and the reason they may evolve into serious competition one day – is to lay them out in separate classes or targets.  This is what I have done below.

Five year anniversary of Nexavar® (sorafenib) approval by FDA

In about two months, five days before Christmas, sorafenib will celebrate five years of approval by the FDA.  When it was approved on December 20th, 2005, for advanced Renal Cell Carcinoma (RCC), it was the first (and is so far the only) approved drug to target B-Raf kinase, a signaling component of the MAPK pathway.  Since then it has also been approved for Hepatocellular Carcinoma (HCC).