Principles of chemotherapy

Question 1

Self-renewal

Answer 1

Generation of more stem cells (Multipotency)

Question 2

Towards differentiation

Answer 2

Unipotency

Question 3

Both pathways (self-renewal and differentiation) are involved in:

Answer 3

Growth, as well as repair and regeneration of tissues

Question 4

As adulthood/maturation is reached, each organ will be made up of a mosaic of both:

Answer 4

Dividing and non dividing cells

Question 5

In final stages of life, (dividing or non dividing cells) may play a greater role in injury responses as cells within the proliferative compartment move towards a permanent quiescent or senescent stage.

Answer 5

Non dividing cells may play a greater role in injury responses

Question 6

senescent cells secrete various factors that can:

Answer 6

Inhibit the ability of neighboring cells to function, and can stimulate the proliferation and malignant progression of nearby cells.

Question 7

What characteristic allows cancer cells to control their own growth?

Answer 7

Cancer cells become masters of their own destinies through autocrine activation of growth receptors like IGF, TGF, EGF, and VEGF.

Question 8

What is autocrine activation in the context of cancer cells?

Answer 8

Autocrine activation is when cancer cells produce growth factors that bind to their own receptors, stimulating pathways that promote cell growth and cycle progression.

Question 9

How does autocrine signaling influence cancer cell behavior?

Answer 9

Autocrine signaling promotes intracellular pathways that lead to the activation and progression of the cell cycle, contributing to cell growth and increased cell size.

Question 10

How do DNA mutations contribute to cancer cells evading growth suppressors?

Answer 10

DNA mutations can alter the structure of proteins such as B-Raf and PI3-kinase, leading to the activation of signaling circuits that promote cell proliferation.

Question 11

Which signaling circuits are often activated due to DNA mutations in cancer cells?

Answer 11

The MAPK (Mitogen-Activated Protein Kinase) and Akt/PKB (Protein Kinase B) pathways are common signaling circuits activated by mutated proteins.

Question 12

What effect do defects in negative-feedback mechanisms have on cancer cell proliferation?

Answer 12

Defects in negative-feedback mechanisms, such as alterations in tumor suppressor genes, enhance proliferative signaling, allowing cancer cells to grow unchecked.

Question 13

Name some tumor suppressor genes that, when altered, contribute to cancer progression.

Answer 13

Key tumor suppressor genes include RB (Retinoblastoma protein) and TP53 (Tumor Protein p53).

Question 14

How do cancer cells avoid detection and destruction by the immune system?

Answer 14

Cancer cells activate negative regulatory pathways that suppress the immune response, making them harder for the immune system to detect and eliminate.

Question 15

What is the role of CTLA-4 in immune evasion by cancer cells?

Answer 15

CTLA-4 is a negative regulator of T-cells, and its activation by cancer cells inhibits T-cell activation, reducing the immune system’s ability to attack cancer cells.

Question 16

Which pathway involves the PD-1/PD-L1/PD-L2 axis in immune evasion?

Answer 16

The PD-1/PD-L1/PD-L2 axis involves receptors on T-lymphocytes that, when activated, send an inhibitory signal that suppresses the immune response.

Question 17

What is the effect of activating the PD-1/PD-L1/PD-L2 pathway on T-cells?

Answer 17

Activation of the PD-1/PD-L1/PD-L2 pathway leads to the production of hyperexhausted effector T-cells, reducing their ability to effectively attack cancer cells.

Question 17

What does “enabling replicative immortality” mean in the context of cancer cells?

Answer 17

It means that cancer cells avoid senescence (aging), bypass the crisis phase, and resist apoptosis (programmed cell death), allowing them to divide indefinitely.

Question 18

What is the key enzyme responsible for enabling replicative immortality in cancer cells?

Answer 18

The enzyme is telomerase, which maintains the length of telomeres and prevents the cell from aging.

Question 19

How does telomerase contribute to the immortality of cancer cells?

Answer 19

Telomerase adds repetitive nucleotide sequences to the ends of chromosomes (telomeres), preventing them from shortening and allowing continuous cell division.

Question 20

Why is telomerase activity considered a hallmark of cancer?

Answer 20

Increased telomerase activity prevents the natural shortening of telomeres, granting cancer cells the ability to replicate indefinitely and sustain tumor growth

Question 21

What are the three main phenotypes of tumor-promoting inflammation?

Answer 21

The three phenotypes are Immune-inflamed, Immune-excluded, and Immune-desert.

Question 22

What characterizes the “Immune-inflamed” phenotype in tumor-promoting inflammation?

Answer 22

It is characterized by the presence of T cells within the tumor parenchyma, close to tumor cells, often showing staining for PD-L1, indicating a pre-existing antitumor immune response that has been arrested.

Question 23

What does the presence of PD-L1 staining in an “Immune-inflamed” tumor suggest?

Answer 23

It suggests that there was an antitumor immune response that became ineffective, likely due to immune checkpoint inhibition.

Question 24

Describe the “Immune-excluded” phenotype

Answer 24

This phenotype is characterized by a high number of immune cells that are unable to penetrate the tumor parenchyma and are instead confined to the stroma surrounding the tumor, indicating a blocked immune response.

Question 25

What does the “Immune-excluded” phenotype suggest about the immune response to the tumor?

Answer 25

It suggests that there is a pre-existing antitumor immune response that is ineffective due to an inability of immune cells to infiltrate the tumor.

Question 26

What defines the “Immune-desert” phenotype in tumor inflammation?

Answer 26

It is characterized by a lack or very low presence of T cells in both the tumor parenchyma and the surrounding stroma, indicating no significant pre-existing antitumor immunity.

Question 27

What does the “Immune-desert” phenotype indicate about the tumor’s immune environment?

Answer 27

It indicates that there is an absence of a pre-existing immune response against the tumor, suggesting a non-inflamed or immune-silent environment.

Question 28

What role does E-cadherin play in cancer, and how does its mutation affect tumor behavior?

Answer 28

E-cadherin is a protein responsible for cell-to-cell adhesion. Mutations in E-cadherin reduce cell adhesion, facilitating cancer cell detachment and increasing the potential for invasion and metastasis

Question 29

How does a mutation in E-cadherin contribute to metastasis?

Answer 29

A mutation in E-cadherin decreases cell adhesion between tumor cells, allowing them to break away from the primary tumor and invade surrounding tissues

Question 30

What is the function of N-cadherin in cancer progression?

Answer 30

N-cadherin is a protein that plays a role in cell movement during processes like organogenesis. In cancer, increased expression of N-cadherin promotes cell migration, aiding in tumor invasion and metastasis.

Question 31

How does a switch from E-cadherin to N-cadherin expression affect cancer cells?

Answer 31

The switch from E-cadherin to N-cadherin (known as the cadherin switch) facilitates cancer cell migration and invasion, leading to enhanced metastatic potential.

Question 32

What role does the extracellular matrix (ECM) play in cancer invasion?

Answer 32

The ECM provides a scaffold for cell adhesion. Alterations in cell-to-ECM adhesion, through changes in ECM production, allow cancer cells to invade and spread to new locations.

Question 33

What is the significance of cell-to-ECM adhesion in metastasis?

Answer 33

Proper cell-to-ECM adhesion is necessary to anchor cells in place. Disruptions in this adhesion enable cancer cells to invade the ECM and migrate to distant sites.

Question 34

What is the difference between vasculogenesis and angiogenesis in the context of cancer?

Answer 34

Vasculogenesis is the formation of new blood vessels from endothelial progenitor cells, while angiogenesis is the sprouting of new blood vessels from existing ones, both processes supporting tumor growth.

Question 35

What triggers angiogenesis in cancer cells?

Answer 35

Angiogenesis is triggered by alterations in endothelial signaling, often mediated by factors like VEGF-A (Vascular Endothelial Growth Factor A) and TSP-1 (Thrombospondin-1).

Question 36

What is the role of VEGF-A in angiogenesis?

Answer 36

VEGF-A promotes the growth of new blood vessels by stimulating endothelial cells to divide and migrate, increasing blood supply to the tumor.

Question 37

How does TSP-1 influence angiogenesis?

Answer 37

TSP-1 is an angiogenesis inhibitor that can suppress the formation of new blood vessels, but its balance with other factors like VEGF-A determines the level of angiogenesis.

Question 38

Which oncogenes are known to enhance angiogenesis in tumors?

Answer 38

Oncogenes such as Ras and Myc enhance angiogenesis by increasing the expression of pro-angiogenic factors like VEGF-A.

Question 39

What effect does the activation of Ras and Myc oncogenes have on endothelial signaling?

Answer 39

Activation of Ras and Myc leads to enhanced expression of VEGF-A, promoting angiogenesis and ensuring a steady blood supply for tumor growth.

Question 40

What is meant by “genome instability and mutation” in the context of cancer?

Answer 40

It refers to the increased rate of mutations in DNA or a higher sensitivity to mutagenic agents due to defects in the mechanisms that maintain genomic integrity.

Question 41

How do mutations in DNA contribute to cancer development?

Answer 41

Mutations can lead to the activation of oncogenes or the inactivation of tumor suppressor genes, promoting uncontrolled cell growth and cancer progression.

Question 42

What can cause an increase in mutations within a cell’s DNA?

Answer 42

Increased mutations can occur due to a breakdown in one or several components of the genomic maintenance machinery, such as DNA damage detection, DNA repair, or inactivation of mutagenic molecules.

Question 43

What role does the genomic maintenance machinery play in preventing cancer?

Answer 43

This machinery is responsible for detecting DNA damage, repairing it, and inactivating or intercepting mutagenic agents to maintain genomic stability.

Question 44

What is the intrinsic caspase pathway, and why is it important for cell death?

Answer 44

The intrinsic caspase pathway is a series of molecular events that lead to programmed cell death (apoptosis) in response to internal stress or damage. It is crucial for eliminating damaged or abnormal cells.

Question 45

How does a mutation in the TP53 gene help cancer cells resist cell death?

Answer 45

A mutation in TP53 can inactivate this tumor suppressor gene, preventing it from initiating apoptosis in response to DNA damage, allowing cancer cells to survive and proliferate despite being damaged.

Question 46

What are Bcl-2 and Bcl-X, and how do mutations in these proteins contribute to cancer?

Answer 46

Bcl-2 and Bcl-X are antiapoptotic regulators that prevent cell death. Mutations that increase their expression or activity block apoptosis, giving cancer cells a survival advantage.

Question 47

How do mutations in IGF (Insulin-like Growth Factor) signaling affect apoptosis in cancer cells?

Answer 47

Mutations in IGF signaling pathways enhance survival signaling, helping cancer cells resist apoptosis and continue growing.

Question 48

What is the main characteristic of deregulated cellular energetics in cancer cells?

Answer 48

Cancer cells often rely on aerobic glycolysis for energy, even in the presence of oxygen, instead of using mitochondrial oxidative phosphorylation, a phenomenon known as the Warburg effect.

Question 49

What is the Warburg effect in cancer cells?

Answer 49

The Warburg effect refers to the preference of cancer cells for aerobic glycolysis, leading to increased glucose uptake and conversion to lactate, even when oxygen is available.

Question 50

How does the Warburg effect benefit cancer cells?

Answer 50

The Warburg effect provides cancer cells with rapid energy (ATP) and supplies building blocks for cell growth and division, contributing to fast tumor proliferation.

Question 51

Why do some cancer cells increase glucose uptake?

Answer 51

Cancer cells increase glucose uptake to fuel aerobic glycolysis, providing energy and essential intermediates for biosynthesis needed for rapid cell division.

Question 52

What are glucose-dependent cells in the context of cancer?

Answer 52

Glucose-dependent cells are subpopulations of cancer cells that rely primarily on glucose for energy production and secrete high levels of lactate as a byproduct of glycolysis.