Chronic cigarette smoking has been associated with several diseases such as lung cancer, COPD, cardiovascular disease and oral cancer in some smokers. While smoking has been known to adversely affect multiple cellular and physiological processes, further research is necessary to understand the aberrant physiology that leads to disease in susceptible individuals following decades of smoking. Appropriate biomarkers indicating smoking effects may enhance this understanding. Ideally, the biomarkers of effect would be able to predict harm from smoking in healthy consumers, and thus identify the at-risk individuals. Further, putative biomarkers might be useful in determining whether consumption of potentially reduced exposure products (PREPs) or modified cigarettes could reduce harm, or allow comparison of tobacco product categories. Therefore, these assessments should be carried out in short-term cell culture assays, animal models and clinical studies. Notwithstanding their promise, very few potential biomarkers of effect are currently available, and several challenges remain. For example, the biomarkers need further qualification, and the methods for their quantification need development and validation. In addition, testing the biomarkers in appropriate experimental models and disease-specific clinical studies will be necessary to rigorously validate them prior to their integration into health assessments.

Current cutting-edge discovery technologies such as transcriptomics, epigenomics and metabolomics, together with an understanding of chemistry and biological consequences of smoking hold promise in the discovery and characterization of biomarkers of effect. Given the complexity of smoking-induced biological changes, a diverse array of biomarkers of effect may emerge. A "fit-for-purpose" strategy may be appropriate for qualifying biomarkers and validating methods to expedite the discovery and characterization of smoking-related biomarkers of effect/harm, and their application for assessing risk to individual consumer and evaluating PREPs.