VAV1

Overview

VAV1 (Vav Guanine Nucleotide Exchange Factor 1) is a RhoGEF that activates Rac/Rho GTPases and functions as an upstream activator of Ras/Raf/RTK signaling. In lung adenocarcinoma, VAV1 mutations are part of an expanded set of Ras/Raf/RTK pathway drivers that raises the fraction of actionable lung ADC cases to 76–85%, particularly in tumors lacking classical EGFR/ALK/ROS1 drivers.

Alterations observed in the corpus

  • Recurrent mutation identified as an expanded RAS-pathway driver in lung adenocarcinoma; inclusion of VAV1 (alongside SOS1, RASA1, ARHGAP35) raises the proportion of lung ADCs with a candidate Ras/Raf/RTK pathway driver to 76% overall in the TCGA Pan-Lung study (1,144 NSCLC cases) PMID:27158780.

Cancer types (linked)

  • LUAD: VAV1 mutations expand the druggable RAS-pathway pool in oncogene-negative lung adenocarcinoma; 85% of expert-reviewed lung ADC subset had a candidate Ras/Raf/RTK driver when VAV1 and related genes were included PMID:27158780.

Co-occurrence and mutual exclusivity

  • No specific co-occurrence or mutual exclusivity data reported in the current corpus.

Therapeutic relevance

  • Inclusion of VAV1 mutations in the Ras/Raf/RTK-pathway driver pool narrows the fraction of lung ADC patients without a candidate targeted therapy; downstream effectors of VAV1-Rac/Rho signaling may represent therapeutic targets PMID:27158780.

Open questions

  • The specific functional impact of observed VAV1 mutations in lung ADC, and whether they activate Ras signaling in a manner analogous to RAS hotspot mutations, requires experimental validation.

Sources

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