Telomerase-positive, Retinoblastoma-defective tumor cells

Telomerase-positive, Retinoblastoma (Rb)-defective tumor cells represent a specific malignant cellular phenotype characterized by the reactivation of telomerase and the loss of functional Rb tumor suppressor signaling. Telomerase activity, primarily through the expression of the human telomerase reverse transcriptase (hTERT), enables cancer cells to bypass replicative senescence by maintaining telomere length (Shay & Wright, 2019, Nature Reviews Genetics). Concurrently, defects in the Rb pathway, often due to mutations in the RB1 gene or hyperactivation of CDK4/6, lead to uncontrolled cell cycle progression from the G1 to the S phase (Sherr & McCormick, 2002, Cancer Cell). This dual phenotype is frequently exploited in the design of oncolytic virotherapies, such as OBP-301 (Telomelysin), which utilizes the hTERT promoter to drive viral replication specifically within these immortalized cells (Kawashima et al., 2004, Clinical Cancer Research). By targeting these specific genetic and biochemical alterations, therapies aim to achieve selective lysis of cancer cells while sparing normal somatic cells that typically lack telomerase activity and possess intact cell cycle checkpoints. This entry is classified as incorrect as a molecular target because it describes a complex cellular state or population rather than a single discrete molecule, receptor, or enzyme.

Other names

hTERT-positive Rb-deficient cancer cellsTelomerase-active Rb-pathway-deficient cellshTERT-expressing Rb-mutant cells

Selective oncolysis mediated by viral replication that is transcriptionally restricted by the hTERT promoter and/or functionally restricted to cells with defective Rb/E2F cell cycle checkpoints.