Predictive biomarkers

Bandaru VV, McArthur JC, Sacktor N, Cutler RG, Knapp EL, Mattson MP, Haughey NJ (2007) Associative and predictive biomarkers of dementia in HIV-l-infected patients. Neurology 68(18) 1481-1487... 

Due to the fact that JP-8 contains hundreds of aliphatic and aromatic hydrocarbons, in addition to various performance additives, this complex mixture poses a serious challenge for risk assessment. Exposure assessment is complicated by the fact that JP-8 may be encountered as a vapor, aerosol, or liquid, and possibly as combustible products, and each physical state may contain different chemical entities. However, progress has been made in the identification of JP-8 components that may serve as reliable and predictable biomarkers of exposure, particularly for dermal exposures [12,35,81,82,83,84],... 

In this emerging era of molecular-targeted therapies, biomarkers are becoming more useful and perhaps even necessary for the success of new drugs. In this context, the two classes of biomarkers that are most relevant are pharmacodynamic biomarkers, which are used to confirm drug activity and mechanism of action, and predictive biomarkers, which are used to predict clinical response to targeted therapies. 

The utilization of pERKl/2 as a predictive biomarker for MEK inhibitors is still unclear. In the phase II trial for CI-1040, archived tumors that dated from months to years before treatment were analyzed for pERKl/2 [134]. 

Despite the limitations of the samples, the data did suggest a correlation between elevated baseline pERKl/2 levels and stable disease. The mutational status of B-Raf is another logical candidate for a predictive biomarker, especially since B-Raf mutations have been shown to confer increased sensitivity to MEKl/2 inhibitors using in vitro and in vivo models [ 135] nothing has yet been reported. 

R5. Regoli, F., Total oxyradical scavenging capacity (TOSC) in polluted and translocated mussels A predictive biomarker of oxidative stress. Aquat. Toxicol. 50, 351-361 (2000). 

In the immediate future, many other common problems of pregnancy and the fetus are likely to be reexamined by proteomics and metabolomics, ultimately identifying the best predictive biomarkers for disease and adverse neonatal outcome. As we have begun to see, pregnancy-induced hypertension (PIH), growth restriction in utero, diabetic pregnancy, and placental insufficiency are but a few of the situations in which early proteomic assessment is likely to play a prominent role in the next several years (Figure 8). 

Outcome based arrays These are the most valuable and most difficult to generate as they involve collation of tissues from patients that have the same disease and have been more or less similarly treated and followed up for a significant period of time. The period of follow-up depends on the type of disease or tumor being studied. These types of arrays are mostly used to evaluate prognostic or predictive biomarkers. The presence of biomarkers in tumor subtypes might then be used to design novel therapeutic strategies. 

A schematic of the flow-through nanohole array concept is shown in Fig. 13a. Figure 13b shows computationally predicted biomarker transport within the nanoholes for in-hole average fluid velocities of 1 pm/s and 1 cm/s (as indicated). Reaction rate constants characteristic of surface-based antibody-antigen reactions (with reaction rate constant k - 10 /M/s) [69] were applied at the nanohole walls. For the low average velocity, diffusion of the biomarker (with diffusivity D - 4x10 m s ) to the nanohole surface is effectively complete in one diameter. This result reflects the rapid diffusion characteristic of nanoconfinement. For the higher flow rate case, the absorption of the analyte stream is delayed however, over 90% bulk adsorption of analyte is attained with the flow rates and nanohole... 

Fig. 13 Integrated flow-through nanohole array concept (a) Schematic of the flow-through nanohole array in a chip-and-reader conflguration (b) Results of computational modeling showing predicted biomarker concentration profiles with through-hole fluid average velocities indicated...

Flirsch R, Dent C, Pfriem FI, Allen J, Beekman RFI, Ma Q, Dastrala S, Bennett M, Mitsnefes M, Devarajan P. NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatr.Nephrol. 2007). 

Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, Edelstein CL, Devarajan P. Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant 2006 7 1639-1645. 

Parikh CR, Mishra J,Thiessen-Philbrook H, et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int 2006 70 199-203. 

NGAL is an early predictive biomarker of contrast-induced nephropathy in children.Pediatr Nephrol. 2007. 

Oguri T, et al. MRP7/ABCC10 expression is a predictive biomarker for the resistance to paclitaxel in non-small cell lung cancer. Mol Cancer Ther. 2008 7 1150-1155. 

Dehdashti F, et al. PET-based estradiol challenge as a predictive biomarker of response to endocrine therapy in women with estrogen-receptor-positive breast cancer. Breast Cancer Res Treat. 2009 113 509-517. 

Dagues N, et al. Investigation of the molecular mechanisms preceding PDE4 inhibitor-induced vasculopathy in rats tissue inhibitor of metalloproteinase 1, a potential predictive biomarker. Toxicol Sci. 2007 100 238-247. 

Kim DH, et al. Elevation of sphinganine 1-phosphate as a predictive biomarker for fumonisin exposure and toxicity in mice. / Toxicol Environ Health A. 2006 69 2071-2082. 

Briefly, BM can be classified as diagnostic biomarkers, which are molecules that help to discriminate between healthy and one or more pathological states prognostic biomarkers are molecules that follow disease evolution. Predictive biomarkers are defined as the molecules that could provide relevant information to predict response or resistance to therapy they also could be used to monitor the response, as well as, in some cases, as diagnostic and prognostic biomarkers. 

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