The purine nucleotides ATP and GTP are essential precursors to DNA and RNA synthesis and fundamental for energy metabolism. Although de novo purine nucleotide biosynthesis is increased in highly proliferating cells, such as malignant tumors, it is not clear if this is merely a secondary manifestation of increased cell proliferation. Suggestive of a direct causative effect includes evidence that, in some cancer types, the rate-limiting enzyme in de novo GTP biosynthesis, inosine monophosphate dehydrogenase (IMPDH), is upregulated and that the IMPDH inhibitor, mycophenolic acid (MPA), possesses anti-tumor activity. However, historically, enthusiasm for employing IMPDH inhibitors in cancer treatment has been mitigated by their adverse effects at high treatment doses and variable response. Recent advances in our understanding of the mechanistic role of IMPDH in tumorigenesis and cancer progression, as well as the development of IMPDH inhibitors with selective actions on GTP synthesis, have prompted a reappraisal of targeting this enzyme for anti-cancer treatment. In this review, we summarize the history of IMPDH inhibitors, the development of new inhibitors as anti-cancer drugs, and future directions and strategies to overcome existing challenges.

Introduction: There are reports that the 12-core template systematic biopsies (SBx) obtained by using software registration machines (e.g., Artemis) have higher cancer detection rates (CDRs) of prostate cancer (PCa) than the standard, freehand 12-core transrectal ultrasound (TRUS)-guided biopsies. The goal of our study is to compare the clinically significant (CS) CDRs of SBx in two independent cohorts who underwent freehand TRUS-SBx alone (Cohort A) or machine-guided SBx as part of a combined MRI-ultrasound (MRI-US) fusion biopsy (FBx) (Cohort B). Materials and Methods: A retrospective review of all patients undergoing prostate biopsies over a 4-year period at the University of Cincinnati Medical Center was performed. CS cancer was defined as having a Gleason score ≥7. MRI-US FBx were obtained by using an Artemis software registration device (ARTEMIS™, Eigen, Inc., Grass Valley, CA). Statistical significance was considered at p < 0.05. Results: Nine hundred and thirty men underwent SBx (Cohort A: 474, Cohort B: 456). There were no statistical differences between cohort A and B in CS CDRs in the overall population (39.3% vs 33.8%; p = 0.093), biopsy naive patients (40.4% vs 39.8%; p = 0.951), or patients with a prior negative biopsy (22.7% vs 25.0%; p = 0.910). Multivariate logistic regression controlling for age, race, prostate-specific antigen level, prostate volume, abnormal digital rectal exam, and family history of PCa demonstrated comparable CS CDRs, which was maintained when further stratified by prior biopsy history (all patients: odds ratio [OR] 0.99, 95% confidence interval [CI] 0.71–1.38, p = 0.958; biopsy naive: OR 0.79, 95% CI 0.51–1.22, p = 0.291; prior negative biopsy: OR 0.64, 95% CI 0.21–1.75, p = 0.403). Conclusions: Our study did not find a significant difference in the CS CDRs of machine-guided SBx compared with the freehand TRUS-SBx. Unless the SBx is done at the time of FBx, the use of these machines for obtaining SBx only is unlikely to result in any increase of CS CDRs.