Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.

A genomics-based approach to identify pharmacodynamic biomarkers was used for a cyclin-dependent kinase inhibitory drug. R547 is a potent cyclin-dependent kinase inhibitor with a potent antiproliferative effect at pharmacologically relevant doses and is currently in phase I clinical trials. Using preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials.

A selective phosphatase of regenerating liver phosphatase inhibitor suppresses tumor cell anchorage-independent growth by a novel mechanism involving p130Cas cleavage.

The phosphatase of regenerating liver (PRL) family, a unique class of oncogenic phosphatases, consists of three members: PRL-1, PRL-2, and PRL-3. Aberrant overexpression of PRL-3 has been found in multiple solid tumor types. Ectopic expression of PRLs in cells induces transformation, increases mobility and invasiveness, and forms experimental metastases in mice.

Genetic association meets RNA interference: large-scale genomic screens for causation and mechanism of complex diseases.

While the genomic era offers great promise for biomedicine in general and for biomarker discovery in particular, it has yet to significantly impact drug target discovery. Meanwhile, despite improvements over the past 20 years in reducing attrition in clinical trials due to adverse drug responses, the pharmaceutical industry continues to be beset by the high rate of attrition of compounds in late-stage development, primarily due to the lack of drug efficacy. Clearly, even highly potent drugs with ideal safety and pharmacokinetic profiles will fail to survive clinical trials if the drug target itself is not a key point of intervention for most patients.

Microarray-based identification of differentially expressed growth- and metastasis-associated genes in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. To improve diagnosis and treatment, key mechanisms of deregulated molecular functions have to be identified. Using microarray analysis, the expression patterns of 5600 human genes were assessed in PDAC by comparison with the normal pancreas and chronic pancreatitis (CP).