Biomarkers of Cancer Risk and Therapeutic Benefit: New Technologies, New Opportunities, and Some Challenges

Abstract

The biotechnology revolution offers unprecedented opportunities for identification of mechanistically-based biomarkers that report and predict cancer and other pathologies. The combination of genomic technologies with a knowledge of gene sequence and sequence conservation has made available markers that facilitate the correlation of genetic variation with biological outcomes, and "-omic" technologies allow efficient biochemical characterization of functional pathways-providing new markers of the susceptibility of individuals to cancer development, and of tumor susceptibility to specific therapies. New therapeutic agents targeted to individuals with specific genetic or biochemical characteristics already exist. The powerful -omic technologies allow efficient monitoring of gene transcripts, proteins, and intermediary metabolites, making it possible to monitor a large number of key cellular pathways simultaneously. This has enabled the identification of key biomarkers and signaling molecules associated with cell growth, cell death, and cellular metabolism. These new markers are facilitating monitoring of functional disturbance, molecular and cellular damage, and damage-response. Improved imaging technologies have made it feasible to image some of these molecular events noninvasively. To meet the challenge of evaluating and developing consensus criteria for the application of these new technologies and biomarkers, consortium approaches are being increasingly undertaken to share resources and to build a common understanding among the research, industry, and regulatory communities. These developments promise more efficient pharmaceutical product development, safer and more efficacious drugs, and provide clinical practitioners with new and better biomarkers for cancer screening, patient monitoring, and choice of therapy.

Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma

“…29,30 Translating a biomarker into clinical practice could reduce patient risk by selecting those most likely to benefit as well as providing an early indicator of response. In developing agents that capitalize on the redox balance in cancer cells, the short-lived ROS molecules create a technical challenge in identifying predictive intermediates.…”