Breast Cancer: Hormone Therapies and Resistance

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Questions and Answers

What occurs during the G2 phase of the cell cycle?

Structures needed for division are made (correct)

DNA is copied

Chromosomes are aligned at the cell equator

Chromatin condenses into chromosomes

Which phase immediately follows G2 in the cell cycle?

M phase (correct)

G1 phase

S phase

Prophase

Which component directly participates in inhibiting the G2/M transition?

Effectors (correct)

Transducers

Sensors

Mediators

Which of the following is crucial for the regulation of the cell cycle at checkpoints?

Cyclins Signup and view all the answers

Which of the following is not a phase of mitosis?

Monophase Signup and view all the answers

What is the role of DNA damage checkpoints in human cells?

Detecting and signaling DNA damage Signup and view all the answers

What percentage of breast cancers will become resistant to hormone therapies?

1 in 3 Signup and view all the answers

What is a consequence of CDK4/6 inhibitors in the treatment of breast cancer?

Blocks phosphorylation of Rb, leading to G1 arrest Signup and view all the answers

Which drug is a CDK4/6 inhibitor?

Ribociclib Signup and view all the answers

What is the effect of adding ribociclib to hormonal therapy in postmenopausal women with HR+ metastatic breast cancer?

Improves progression-free survival by 44% Signup and view all the answers

How much did the sales of Palbociclib increase from 2017 to 2018?

51.7% Signup and view all the answers

What is one of the primary mechanisms causing resistance to hormone therapies in breast cancer?

Crosstalk between intracellular signalling pathways Signup and view all the answers

What was the total sales amount of Palbociclib in 2018?

$4.118 billion Signup and view all the answers

What is the main function of estrogen receptor alpha when bound by estrogen?

Triggers gene transcription Signup and view all the answers

Which phase of the cell cycle involves DNA replication?

S Signup and view all the answers

In which sub-phase of mitosis does the cell's nucleus divide?

Karyokinesis Signup and view all the answers

What occurs during the G1 phase of the cell cycle?

Cell growth and synthesis of organelles Signup and view all the answers

What is the purpose of the S-phase DNA-damage checkpoint?

To double-check duplicated chromosomes for errors Signup and view all the answers

Which stage of the cell cycle directly results in the formation of two daughter cells?

Cytokinesis Signup and view all the answers

Which of the following is not a phase of interphase?

M Signup and view all the answers

What is the primary activity in the G2 phase of the cell cycle?

Cell growth and preparation for mitosis Signup and view all the answers

When does the cell 'double check' the duplicated chromosomes for errors?

S-phase Signup and view all the answers

Study Notes

Treatment Resistant Breast Cancer

1 in 3 breast cancers become resistant to hormone therapies due to crosstalk between intracellular signalling pathways.
Combination therapy with CDK4/6 inhibitors, such as ribociclib and palbociclib, may offer a solution.

CDK4/6 Inhibitors

CDK4/6 inhibitors block phosphorylation of Rb, leading to G1 arrest.
They decrease the appearance of resistance to hormonal chemotherapy.

Estrogen Receptor Signalling

The main ER pathway involves estrogen binding to estrogen receptor a, triggering gene transcription.
The secondary ER pathway is also involved.

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%.
Palbociclib also improves PFS and overall response to therapy.

Cell Cycle

The cell cycle is the series of events leading to cell division and duplication.
It involves DNA replication, growth, and preparation for cell division.

Phases of the Cell Cycle

Interphase: G1, S, G2 phases, where the cell grows and prepares for cell division.
Mitosis (M-phase): Karyokinesis (nuclear division) and Cytokinesis (cytoplasmic division).

Sub-phases of the Cell Cycle

G1: primary growth phase, cell grows and synthesizes proteins and organelles.
S: synthesis phase, DNA is replicated.
G2: secondary growth phase, cell continues to grow and prepares for mitosis.
M: mitosis, replicated chromosomes are separated and distributed to daughter cells.
C: cytokinesis, cytoplasm divides, forming two daughter cells.

DNA Replication

DNA is replicated in S-phase, and errors are checked and repaired.
Each of the 46 chromosomes is duplicated by the cell.

G1 and G2 Phases

G1: integrity of DNA is checked, damage is repaired, and checkpoint R ensures proper progression.
G2: structures needed for division are made, and the G2-phase checkpoint ensures correct chromosome complement and checks for DNA damage.

Mitosis Phase

Prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis occur in sequence.

Control of Cell Cycle Progression

The cell cycle is regulated by checkpoints controlled by a family of proteins, including cyclins and cyclin-dependent kinases (Cdks).

Cell Cycle Regulation

Cyclins and Cdks regulate the cell cycle.
Checkpoints, including DNA damage and replication stress, control cell cycle progression.

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Description

This quiz covers the mechanisms of treatment resistant breast cancer, including crosstalk between intracellular signalling pathways and the role of CDK4/6 inhibitors in overcoming resistance to hormone therapies. Topics include Ribociclib, Palbociclib, and estrogen receptor signalling.