Yap governs a lineage-specific neuregulin1 pathway-driven adaptive resistance to RAF kinase inhibitors.

Background: Inactivation of the Hippo pathway promotes Yap nuclear translocation, enabling execution of a transcriptional program that induces tissue growth. Genetic lesions of Hippo intermediates only identify a minority of cancers with illegitimate YAP activation. Yap has been implicated in resistance to targeted therapies, but the mechanisms by which YAP may impact adaptive resistance to MAPK inhibitors are unknown.

Oncogenic Pathways in Neurodegenerative Diseases.

Cancer and neurodegenerative diseases are two of the leading causes of premature death in modern societies. Their incidence continues to increase, and in the near future, it is believed that cancer will kill more than 20 million people per year, and neurodegenerative diseases, due to the aging of the world population, will double their prevalence. The onset and the progression of both diseases are defined by dysregulation of the same molecular signaling pathways.

Comprehensive Genetic Characterization of Human Thyroid Cancer Cell Lines: A Validated Panel for Preclinical Studies.

Purpose: Thyroid cancer cell lines are valuable models but have been neglected in pancancer genomic studies. Moreover, their misidentification has been a significant problem. We aim to provide a validated dataset for thyroid cancer researchers.

Tipifarnib Inhibits HRAS-Driven Dedifferentiated Thyroid Cancers.

Of the three RAS oncoproteins, only HRAS is delocalized and inactivated by farnesyltransferase inhibitors (FTI), an approach yet to be exploited clinically. In this study, we treat mice bearing Hras-driven poorly differentiated and anaplastic thyroid cancers ( ) with the FTI tipifarnib. Treatment caused sustained tumor regression and increased survival; however, early and late resistance was observed.