| First Author | Herrero A | Year | 2015 |
| Journal | Cancer Cell | Volume | 28 |
| Issue | 2 | Pages | 170-82 |
| PubMed ID | 26267534 | Mgi Jnum | J:230602 |
| Mgi Id | MGI:5763344 | Doi | 10.1016/j.ccell.2015.07.001 |
| Citation | Herrero A, et al. (2015) Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes. Cancer Cell 28(2):170-82 |
| abstractText | Nearly 50% of human malignancies exhibit unregulated RAS-ERK signaling; inhibiting it is a valid strategy for antineoplastic intervention. Upon activation, ERK dimerize, which is essential for ERK extranuclear, but not for nuclear, signaling. Here, we describe a small molecule inhibitor for ERK dimerization that, without affecting ERK phosphorylation, forestalls tumorigenesis driven by RAS-ERK pathway oncogenes. This compound is unaffected by resistance mechanisms that hamper classical RAS-ERK pathway inhibitors. Thus, ERK dimerization inhibitors provide the proof of principle for two understudied concepts in cancer therapy: (1) the blockade of sub-localization-specific sub-signals, rather than total signals, as a means of impeding oncogenic RAS-ERK signaling and (2) targeting regulatory protein-protein interactions, rather than catalytic activities, as an approach for producing effective antitumor agents. |
