Asparagine synthetase: a new potential biomarker in ovarian cancer.
L-Asparaginase (L-ASP) is an enzyme drug that has been an asset to leukemia treatment regimens for four decades. Variability in its clinical efficacy, however, has prompted the search for biomarkers capable of distinguishing responders from non-responders. In that regard, the NCI-60 cell line panel has served as a biomarker discovery platform and has led to the identification of a correlation between L-ASP efficacy and asparagine synthetase (ASNS) expression in cultured cells. The presence of that correlation in the ovarian subpanel of the NCI-60 has made a case for repositioning L-ASP to ovarian cancer. This review presents an overview of the biomarker development process, summarizes the efforts that have been invested thus far in developing ASNS as a biomarker for ovarian cancer treatment, highlights the role of RNAi and the limitations of the NCI-60 in that process, and addresses important considerations for next steps in the development of ASNS as a predictive biomarker.
Lorenzi
Philip L
PL
Genomics & Bioinformatics Group, Laboratory of Molecular Pharmacology, Center for Cancer Research (CCR), National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. lorenzip@mail.nih.gov
Weinstein
John N
JN
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001215:Asparaginase / Q000494:pharmacology / Q000627:therapeutic use; D001217:Aspartate-Ammonia Ligase / Q000032:analysis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011237:Predictive Value of Tests; D034622:RNA Interference
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D001215:Asparaginase; D001217:Aspartate-Ammonia Ligase