Cell cycle and survival regulators

Cell cycle and survival regulators refers to a broad functional class of proteins that orchestrate the eukaryotic cell cycle and the intrinsic/extrinsic pathways of apoptosis (Hanahan & Weinberg, 2011). This category includes key enzymes such as cyclin-dependent kinases (CDKs), which act as the engine of the cell cycle, and the BCL-2 family of proteins, which serve as the primary gatekeepers of the intrinsic apoptotic pathway (Sherr et al., 2016; Czabotar et al., 2014). Other notable members include the p53 tumor suppressor and its negative regulator MDM2, which integrate stress signals to decide between cell cycle arrest and apoptosis (Khoury & Bürglin, 2016). In many pathological states, particularly oncology, these regulators are frequently dysregulated via gene amplification, mutation, or epigenetic changes, allowing for unchecked cellular proliferation and resistance to death signals (NCI, 2023). Therapeutic strategies targeting these pathways have led to the development of highly successful drugs, such as CDK4/6 inhibitors (e.g., Palbociclib) for breast cancer and BCL-2 inhibitors (e.g., Venetoclax) for hematologic malignancies (Finn et al., 2016; Roberts et al., 2016). Because these regulators are also vital for the homeostasis of normal tissues, such as the bone marrow, pharmacological inhibition often results in predictable toxicities like myelosuppression and neutropenia (FDA, 2021).

Other names

Cell cycle control proteinsApoptosis and cell cycle regulatorsPro-survival and proliferative factorsCell cycle and survival pathways

Inhibition of cyclin-dependent kinases (CDKs) to induce cell cycle arrest; inhibition of anti-apoptotic proteins (e.g., BCL-2) to promote programmed cell death; modulation of checkpoint proteins to restore normal growth control.