Konstantinos J. Mavrakis1, Ellice McDonald1, Michael R. Schlabach1, Éric Billy2, Gregory R. Hoffman1, Antoine de Weck2, David A. Ruddy1, K. Venkatesan1, Jianjun Yu3, Gregg McAllister1, Mark Stump1, Rosalie deBeaumont1, Samuel B. Ho1, Yiyang Yue1, Yue Liu1, Yan Yan‐Neale1, Guizhi Yang1, Fallon Lin1, Hong Yin1, Hui Gao1, D. Randal Kipp1, Songping Zhao1, Joshua T. McNamara1, Elizabeth R. Sprague1, Bing Zheng3, Ying Lin4, Young Shin Cho1, Justin Gu4, Kenneth Crawford3, David N. Ciccone1, Alberto C. Vitari3, Albert Lai3, Vladimı́r Čápka1, Kristen E. Hurov1, Jeffery A. Porter1, John A. Tallarico1, Craig Mickanin1, Emma Lees1, Raymond Pagliarini1, Nicholas Keen1, Tobias Schmelzle2, Francesco Hofmann2, Frank Stegmeier1, William R. Sellers1
1Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA
2Novartis Institutes for BioMedical Research, Basel CH-4002, Switzerland
3Novartis Institutes for BioMedical Research, Emeryville, CA 94608, USA
4China Novartis Institutes for Biomedical Research, Shanghai 201203, China.
Tóm tắt
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
