Webinar Report: Impact of Next Generation/Whole-Genome Sequencing on Companion Diagnostics

Biomarkers are increasingly part of pharmaceutical and clinical strategy.  By some estimates, the success rate of FDA approval of new cancer drugs is 75% if mechanism-of-action and predictive or prognostic biomarkers are clearly defined, whereas it is 25% without the biomarker information.  However, identifying new biomarkers for companion diagnosis (CDx) remains a challenge—the identification of KRAS-type biomarkers is rare, there is a double regulatory hurdle and revenue issues hamper pharmaceutical investment in this area.  Whole-genome sequencing is an important tool in the discovery of biomarkers. 

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.