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Questions and Answers
What proteins are involved in the regulation of the cell cycle?
What happens when cyclin is present in the cell cycle?
Which phase is directly started by activating Cdk through cyclin?
What components are involved in the DNA damage checkpoints in human cells?
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During which cell cycle checkpoint can DNA damage be repaired?
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How does resistance to hormone therapies develop in breast cancer?
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What drug is part of the next new wave for treating breast cancer?
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What role do sensors play in the DNA damage checkpoints?
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During which phase of the cell cycle is DNA replicated?
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What happens during the G1 phase of interphase?
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Which checkpoint ensures the integrity of the DNA and repairs damage in the G1 phase?
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Which phase includes the processes of prophase, metaphase, anaphase, and telophase?
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What major event occurs during the G2 phase?
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The S-phase DNA-damage checkpoint is responsible for checking for errors during which process?
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What is the main function of the estrogen receptor alpha in its signaling pathway?
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Which intracellular component is specifically associated with the estrogen receptor alpha pathway?
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What effect does blocking the phosphorylation of Rb have, as caused by CDK4/6 inhibitors like ribociclib and palbociclib?
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What is a primary benefit of adding ribociclib to hormonal therapy in postmenopausal women with HR+ metastatic breast cancer?
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Which pathway does the G protein-coupled estrogen receptor primarily affect?
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Study Notes
Cell Cycle Regulation
- The cell cycle is regulated by checkpoints, which are controlled by a highly conserved family of proteins, including cyclins, cyclin-dependent kinases (Cdks), and checkpoints.
- Cell cycle progression is controlled by the presence or absence of cyclin, which activates or inhibits Cdk.
Cell Cycle Progression
- When cyclin is present, Cdk is activated, phosphorylating six/five targets, and S phase begins, activating DNA replication enzymes.
- When there is no cyclin, Cdk is inactive, and S phase factors are "off."
Cell Cycle Regulation: Checkpoints
- Checkpoints involve several components, including DNA damage, replication stress, signals, sensors, transducers, and effectors.
- DNA damage is detected by sensors that transduce the signal to transducers, which activate or inactivate effectors that directly participate in inhibiting the G1/S transition, S-phase progression, or the G2/M transition.
Cell Cycle Checkpoint Control
- Cell cycle checkpoint control involves several steps:
- DNA damage is detected
- DNA damage can be repaired during G2/M
- DNA damage can be repaired during Anaphase to Cytokinesis
- Cyclin is inhibited, and the cell cycle is inhibited
Treatment Resistant Breast Cancer
- 1 in 3 breast cancers will become resistant to hormone therapies
- Resistance is due to crosstalk between intracellular signalling pathways
- Cdk 4/6 inhibitors are a new wave of breast cancer drugs
- Estrogen Receptor Signaling has two main pathways:
- Main Pathway: Estrogen Receptor alpha, transcription factor, and Estrogen response element
- Secondary Pathway: G protein-coupled estrogen receptor, activates multiple intracellular signaling pathways
Cdk 4/6 Inhibitors
- Ribociclib and Palbociclib are CDK4/6 inhibitors
- They block phosphorylation of Rb, leading to G1 arrest
- Decreases the appearance of resistance to hormonal chemotherapy
Combination Therapy
- Adding ribociclib to hormonal therapy in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer improves progression-free survival (PFS) by 44% and significantly improves overall response to therapy.
The Cell Cycle
- The cell cycle is the process by which a cell grows, replicates its DNA, and divides into two daughter cells.
- The cell cycle consists of five phases: G1, S, G2, M, and C.
Phases of the Cell Cycle
- G1: Primary growth phase, during which additional organelles are synthesized and the cell carries on its normal metabolic activities.
- S: Synthesis phase, during which DNA is replicated.
- G2: Secondary growth phase, during which structures needed for division are made.
- M: Mitosis, during which nuclear division occurs.
- C: Cytokinesis, during which the cytoplasm divides, and the cell splits into two daughter cells.
Interphase
- Interphase consists of G1, S, and G2 phases.
- It is followed by Mitosis (M) and Cytokinesis (C).
- Interphase G1 has a checkpoint, R (Restriction point), where the integrity of the DNA is checked, and damage is repaired.
- Interphase G2 has a checkpoint that ensures correct chromosome complement and checks for DNA damage.
- S-phase has a DNA-damage checkpoint.
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Description
Learn about the regulation of cell cycle progression through checkpoints, cyclins, and cyclin-dependent kinases.
