RAS-pathway–activated tumor cells

RAS-pathway–activated tumor cells are malignant cells characterized by the constitutive activation of the Ras/Raf/MEK/ERK signaling cascade, often due to gain-of-function mutations in RAS genes such as KRAS, HRAS, or NRAS [1]. This pathway serves as a central regulator of cell growth, differentiation, and survival, and its dysregulation is a hallmark of approximately 30% of all human cancers, including pancreatic, colorectal, and lung carcinomas [2]. In these cells, the activated RAS pathway provides a survival advantage by promoting uncontrolled proliferation and inhibiting programmed cell death [3]. A unique therapeutic vulnerability of these cells is their susceptibility to certain oncolytic viruses, such as Pelareorep (a proprietary formulation of reovirus) [4]. In normal cells, viral infection triggers the activation of double-stranded RNA-activated protein kinase (PKR), which halts protein synthesis and prevents viral replication; however, in RAS-pathway–activated tumor cells, RAS signaling inhibits PKR, allowing the virus to replicate selectively, lyse the host cell, and stimulate a systemic anti-tumor immune response [5]. Consequently, these cells serve as the primary target for oncolytic therapies and various small-molecule inhibitors designed to disrupt oncogenic signaling [6].

Other names

RAS-transformed cellsRAS-mutant tumor cellsRAS-activated cancer cellsRAS-pathway-activated cells

Selective oncolytic viral replication and cell lysis facilitated by RAS-mediated suppression of the PKR-dependent antiviral response [4, 5].