We have been collaborating with Dr. Curtis Harris and the Laboratory of human carcinogenesis on discovery of cancer biomarkers using human specimens and our mouse cancer bioassays. Collaboration with Curtis Harris: Purpose: Non-smokers account for 10-13% of all lung cancer cases in the United States. Etiology is attributed to multiple risk factors including exposure to secondhand smoking, asbestos, environmental pollution, and radon, but these exposures are not within the current eligibility criteria for early lung cancer screening by low-dose computed tomography (LDCT). Experimental design: Urine samples were collected from two independent cohorts comprising 846 participants (exploratory cohort) and 505 participants (validation cohort). The cancer urinary biomarkers, creatine riboside (CR) and N-acetylneuraminic acid (NANA) were analyzed and quantified using liquid chromatography-mass spectrometry to determine if non-smoker cases can be distinguished from sex and age-matched controls in comparison to tobacco smoker cases and controls, potentially leading to more precise eligibility criteria for LDCT screening. Results: Urinary levels of CR and NANA were significantly higher and comparable in non-smokers and tobacco smoker cases as compared to population controls in both cohorts. Receiver Operating Characteristics (ROC) analysis for combined CR and NANA levels in non-smokers of the exploratory cohort resulted in better predictive performance with the area under the curve (AUC) of 0.94, whereas the validation cohort non-smokers had an AUC of 0.80. Kaplan-Meier survival curves showed that high levels of CR and NANA were associated with increased cancer-specific death in non-smokers as well as tobacco smoker cases in both cohorts. Conclusions: Measuring CR and NANA in urine liquid biopsies could identify non-smokers at high risk for lung cancer as candidates for LDCT screening and warrant prospective studies of these biomarkers. We are starting a new study to discover biomarkers for metastatic prostate cancer in collaboration with Dr. William Figg and the Genitourinary Malignancies Branch, and Walter Reed Hospital.