Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Novel molecular markers for cancer progression are valuable for the diagnosis and evaluation of treatment efficacies of the diseases. Expression of inosine 5'-monophosphate dehydrogenase type II (IMPDH2), a rate-limiting enzyme in the de novo guanine nucleotide biosynthesis, is up-regulated in various neoplasms, including prostate cancer and patient serum. However, whether IMPDH2 can serve as a biomarker for other urologic cancers is unknown. Paired patient tissue macroarrays were analyzed by immunohistochemistry, the IMPDH2 protein expression in these tissues was quantitated and expressed as immunoreactivity scores. Compared with non-cancerous tissues, IMPDH2 protein expression levels were significantly upregulated in kidney and bladder cancer, but no difference in testis cancer. In addition, expression of IMPDH2 was not associated with the disease clinical stages and pathological features. The findings suggest that overexpressed IMPDH2 can be used as a biomarker for kidney and bladder cancer diagnosis and is a potential therapeutic target for the diseases.
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PMID:Elevated expression of IMPDH2 is associated with progression of kidney and bladder cancer. 2546 60

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.
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PMID:Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story. 3151 46