Affiliation:
1. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
2. The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Abstract
Tumors put in a vulnerable position
Cancer cells often display alterations in metabolism that help fuel their growth. Such metabolic “rewiring” may also work against the cancer cells, however, by creating new vulnerabilities that can be exploited therapeutically. A variety of human tumors show changes in methionine metabolism caused by loss of the gene coding for 5-methylthioadenosine phosphorylase (MTAP). Mavrakis
et al.
and Kryukov
et al.
found that the loss of MTAP renders cancer cell lines sensitive to growth inhibition by compounds that suppress the activity of a specific arginine methyltransferase called PRMT5. Conceivably, drugs that inhibit PRMT5 activity could be developed into a tailored therapy for MTAP-deficient tumors.
Science
, this issue pp.
1208
and
1214
Funder
Novartis Institutes for BioMedical Research
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
Melanoma Research Alliance
NIH PO1 Research Program
Integrative Cancer Biology Program
Conquer Cancer Foundation
2014 AACR-Bristol-Myers Squibb Oncology Fellowship in Clinical Cancer Research
arin Grunebaum Cancer Research Foundation
National Center for Research Resources
National Center for Advancing Translational Sciences
NIH
Publisher
American Association for the Advancement of Science (AAAS)
Reference33 articles.
1. Genomic cloning of methylthioadenosine phosphorylase: a purine metabolic enzyme deficient in multiple different cancers.
2. Gene deletion chemoselectivity: Codeletion of the genes for p16(INK4), methylthioadenosine phosphorylase, and the alpha- and beta-interferons in human pancreatic cell carcinoma lines and its implications for chemotherapy;Chen Z. H.;Cancer Res.,1996
3. Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas;Illei P. B.;Clin. Cancer Res.,2003
4. Homozygous deletion of the MTAP gene in invasive adenocarcinoma of the pancreas and in periampullary cancer: A potential new target for therapy
5. Concordant Loss of MTAP and p16/CDKN2A Expression in Gastroesophageal Carcinogenesis
Cited by
404 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献