Rasdependent

Rasdependent is a term used in molecular biology to describe cellular processes, phenotypes, or states that require signaling through the Ras family of small GTPases for initiation or maintenance. Rasdependent processes rely on Ras cycling between active GTP-bound and inactive GDP-bound forms, typically triggered by receptor tyrosine kinases upon growth factor stimulation.

Activated Ras engages several downstream effector pathways, most notably the RAF-MEK-ERK (MAPK) cascade, the PI3K-AKT pathway, and the RalGEF-Ral axis. The specific combination of effectors engaged, together with the cellular context, determines the Rasdependent outcome, which can include proliferation, differentiation, survival, or migration.

Rasdependency is a prominent concept in cancer biology. Many cancers harbor activating mutations in KRAS, NRAS, or HRAS that confer constitutive Ras signaling, making tumor cells Rasdependent for growth and survival in certain contexts. Therapeutic strategies often target downstream nodes of Ras signaling, such as MEK, ERK, or PI3K pathways, to exploit this dependency. Conversely, some tumors adapt alternative signaling routes and become Ras-independent, contributing to therapeutic resistance and heterogeneity.

Assessing Rasdependency in experimental systems typically involves genetic ablation or silencing of Ras genes, expression of dominant-negative Ras mutants, or the use of pharmacological inhibitors, followed by measurements of cell viability, proliferation, and signaling activity. As a term, Rasdependent is used to denote reliance on Ras-driven signaling, while acknowledging isoform- and context-specific variability. See also Ras signaling, MAPK pathway, and oncogene addiction.