Ras: structural details to guide direct targeting

Ras: structural details to guide direct targeting

These proteins are mutated in about 20% of all human cancers and are thus important targets for drug discovery [1]. Major efforts over the last 20 years have not yielded drugs, promoting the notion that Ras is undruggable [2]. Recent advances in the structural biology of Ras provide new venues to be explored. The crystal structure of Ras has been known for over 25 years. Structural rearrangemen...

'Pathway drug cocktail': targeting Ras signaling based on structural pathways.

Tumors bearing Ras mutations are notoriously difficult to treat. Drug combinations targeting the Ras protein or its pathway have also not met with success. 'Pathway drug cocktails', which are combinations aiming at parallel pathways, appear more promising; however, to be usefully exploited, a repertoire of classified pathway combinations is desirable. This challenge would be facilitated by the ...

Targeting Ras in myeloid leukemias.

Ras proteins normally relay growth-promoting signals from many activated cell surface receptors, and they are altered by oncogenic point mutations in approximately 30% of human cancers. Activating KRAS and NRAS mutations are especially common in malignancies of the pancreas, lung, and colon, and in myeloid leukemia. Here, we discuss general strategies for targeting hyperactive Ras signaling in ...

A Beginner's Guide to Structural Equation Modeling

A Brief Guide to Structural Equation Modeling

To complement recent articles in this journal on structural equation modeling (SEM) practice and principles by Martens and by Quintana and Maxwell, respectively, the authors offer a consumer’s guide to SEM. Using an example derived from theory and research on vocational psychology, the authors outline six steps in SEM: model specification, identification, data preparation and screening, estimat...