Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets.

ABSTRACT: Replication stress (RS) is a characteristic state of cancer cells as they tend to exchange precision of replication for fast proliferation and increased genomic instability. To overcome the consequences of improper replication control, malignant cells frequently inactivate parts of their DNA damage response (DDR) pathways (the ATM-CHK2-p53 pathway), while relying on other pathways which help to maintain replication fork stability (ATR-CHK1). This creates a dependency on the remaining DDR pathways, vulnerability to further destabilization of replication and synthetic lethality of DDR inhibitors with common oncogenic alterations such as mutations of TP53, RB1, ATM, amplifications of MYC, CCNE1 and others. The response to RS is normally limited by coordinati

SUBMITTER: Khamidullina AI 

PROVIDER: S-EPMC10816012 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature