Friday, February 25, 2011

HiJAKing the JAKs in Myeloproliferative Disorders

Myeloproliferative neoplasms (MPNs) are characterized by uncontrolled proliferation of differentiated myeloid cells in the bone marrow, and have an underlying clonal genetic change.  They often evolve into acute myelogenous leukemia (AML).  MPNs with chromosomal translocation t(9;22) BCR-ABL, also called Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML), have a very good prognosis.  Imatinib (Gleevec; Novartis) is a very effective inhibitor of BCR-ABL kinase.  On the other hand, Ph-negative MPNs, until recently had lacked targeted approaches.  This changed in 2005 with the discovery of a dominant gain-of-function somatic mutation in Janus Kinase-2 (JAK2) of a significant proportion of MPNs, wherein guanine-to-thymidine substitution results in a valine-to-phenylalanine change at position 617.  

Friday, February 18, 2011

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.  

Friday, February 11, 2011

Friday Grand Rounds: Harold Varmus Discusses Cancer Cell Biology and Clinical Translation

Thirty-five years ago Harold E. Varmus [wikipedia], along with J. Michael Bishop, discovered the role of oncogenes in cancer.  That seminal discovery in 1975 gave cancer researchers a path, "the road to be taken," that has today led to great advancements in clinical oncology; it has changed the face of a growing number of cancer types to potentially curable or manageable forms.  Not long ago, both scientists were honored with the Nobel Prize in Medicine in 1989 [read, [here, here]

Sunday, February 6, 2011

Oncology Focused Pharmacogenomic "predictive" Biomarkers

Pharmacogenetics and pharmacogenomics (abbreviated together as PGx) are key to the future of personalized medicine.  Pharmacogenomic biomarkers provide tools to predict (a) drug response or (b) adverse drug reactions.  Such biomarkers help to maximize efficacy and minimize toxicity. 

Tuesday, February 1, 2011

Astellas Oncology: Dora's Estrellas in Astellas' Star-Pocket

Many of you may recall the spring of 2010 when Astellas tried to acquire OSI Pharmaceuticals - the barbs flew, as expected, until tons of Yens (to the tune of $4B) were offered to calm OSI and bring it into the Astelles family.  That event signaled the maturing of Astellas as an oncology firm.