Targeting K-Ras cancers

Pl1: Targeting K-ras Driven Lung and Pancreatic Tumors

Molecular pathways: targeting the dependence of mutant RAS cancers on the DNA damage response.

Of the genes mutated in cancer, RAS remains the most elusive to target. Recent technological advances and discoveries have greatly expanded our knowledge of the biology of oncogenic Ras and its role in cancer. As such, it has become apparent that a property that intimately accompanies RAS-driven tumorigenesis is the dependence of RAS-mutant cells on a number of nononcogenic signaling pathways. ...

mTOR Co-Targeting in Cetuximab Resistance in Head and Neck Cancers Harboring PIK3CA and RAS Mutations

BACKGROUND Cetuximab, a monoclonal blocking antibody against the epidermal growth factor receptor EGFR, has been approved for the treatment of squamous cell carcinomas of the head and neck (HNSCC). However, only few patients display long-term responses, prompting the search for cetuximab resistance mechanisms and new therapeutic options enhancing cetuximab effectiveness. METHODS Cetuximab-sen...

Molecular Pathways Molecular Pathways: Targeting the Dependence of Mutant RAS Cancers on the DNA Damage Response

Of the genesmutated in cancer,RAS remains themost elusive to target. Recent technological advances and discoveries have greatly expanded our knowledge of the biology of oncogenic Ras and its role in cancer. As such, it has become apparent that a property that intimately accompanies RAS-driven tumorigenesis is the dependence of RAS-mutant cells on a number of nononcogenic signaling pathways. The...

Role of autophagy in K-RAS- and B-RAF-driven lung cancers

Autophagy degrades and recycles proteins and organelles to support metabolism and survival starvation. Oncogenic RAS upregulates autophagy required for mitochondrial function, stress survival, and engrafted tumor growth. We deleted an essential autophagy gene, autophagy-related-7 (Atg7), concurrently with Kras activation with or without intact Trp53 in two mouse models for non-small-cell lung c...