AKR1B10 and its emerging role in tumor carcinogenesis and as a cancer biomarker

I read with great interest the recent article by Ma et al. in a recent issue of your esteemed journal.1 The article is highly thought provoking. Interestingly, new data have recently emerged over the past few years that implicate AKR1B10 in tumor carcinogenesis in different systemic malignancies besides breast carcinomas. For instance, increased expression of AKR1B10 is seen in nearly 84% of squamous cell pulmonary carcinomas.2 In fact, a close co-relation exists between AKR1B10 expression by lung cancers and smoking habits.3 AKR1B10 is therefore rapidly emerging as a sensitive marker of nonsmall cell lung carcinomas especially in smokers.4 Similarly, AKR1B10 alters prenylation of pancreatic proteins. As a result, tumor carcinogenesis is accentuated in pancreatic carcinomas. In fact, 70% of pancreatic adenocarcinomas demonstrate increased AKR1B10 expression, thus making AKR1B10 a potential biomarker of pancreatic malignancies.5 AKR1B10 is also emerging as a prognostic biomarker of hepatocellular carcinomas. For instance, a better prognostic outcome is seen with accentuated AKR1B10 expression.6 Increased AKR1B10 expression is especially associated with underlying cirrhosis and viral-mediated hepatocellular carcinomas. AKR1B10 expression also serves as a prognostic biomarker of bladder carcinogenesis. For instance, postcystectomy patients who receive dual gemcitabine and carboplatin therapy and express AKR1B10 generally tend to have a poor clinical outcome.7 Attenuated AKR1B10 expression in colonic tissue also serves as a marker of carcinogenesis in these tissues. In fact, downregulated AKR1B10 levels are seen in nearly 88% of colorectal carcinomas.8 Simultaneous attenuation of AKR1B1 is seen in 10% of colorectal carcinomas. Bortezomib causes upregulation of AKR1B10, and this finding may explain its potential chemotherapeutic role in colorectal carcinomas.9 The above examples clearly illustrate the role of AKR1B10 in tumor carcinogenesis and the need for further large-scale studies to fully elaborate its role and prognostic significance in other tumors. Yours sincerely, Shailendra Kapoor