In the last decade progress has been made in oncology successfully tailoring Selleck BcrAbl inhibitor treatments based on molecular markers. In breast cancer patients, overexpression of the HER2/neu protein is associated with more aggressive growth but also predicts response to trastuzumab therapy. In non small cell lung cancer, EGFR mutation is predictive of response to erlotinib therapy and in colon cancer,

K-ras mutation predicts response to monoclonal antibodies to EGFR. Historically, the pharmaceutical companies developed medications based upon empiric observations, thereby subjecting all patients to the toxicities of the medication. Now in the era of genomic research, technologies have Inhibitors,research,lifescience,medical been developed to probe the cancer genome searching for the driving mechanisms

of cancer growth. And yet, currently we only have Inhibitors,research,lifescience,medical a few predictive markers of treatment response. Many studies have been published examining biomarkers and confusion often arises between prognostic and predictive biomarkers. Prognostic markers assess the risk of disease recurrence and outcome for marker positive versus negative patients independent of the treatment. A predictive marker compares treatment outcome based upon marker positive versus negative. In evaluating the predictive nature of a biomarker, many studies rely on banked specimens, which may Inhibitors,research,lifescience,medical lead to selection bias or underpowered analysis. For instance, various studies have shown that patients with cancers overexpressing thymidylate synthase (TS) had a worse outcome compared to those with lower levels of TS. However, results regarding levels of TS as a marker of benefit from adjuvant chemotherapy using Inhibitors,research,lifescience,medical 5-FU have been conflicting (2),(3). In validating a biomarker,

utilization of specimens collected from large phase 3 clinical trials randomizing patients between an experimental therapy versus control treatment helps minimize bias. Ideally a confirmatory trial should be designed testing all patients for the biomarker prior to treatment Inhibitors,research,lifescience,medical and then evaluating until outcomes based upon therapy. The study by Katkoori VR et al (4) in the current issue analyzed the predictive value of Bax, Bcl-2, and p53. The BCL-2 family, including its antiapoptotic and proapoptotic members, plays a central role in the regulation of cell death. Bax protein, located in the outer mitochondrial membrane, is a key promoter of apoptosis. Overexpression of Bax induces increased mitochondrial permeability, which leads to the release of cytochrome c. Cytochrome c, together with other effectors, induces cleavage of caspase, which leads to the degradation of the chromosomal DNA and triggers the execution of apoptosis (5). The study by Katkoori VR et al (4) is attempting to determine their association with survival in colorectal cancer patients treated with 5-FU based adjuvant therapy after surgery.