Seminal Articles

Question 1

What is sustained proliferative signaling?

Answer 1

Sustained proliferative signaling allows cancer cells to maintain chronic proliferation by deregulating growth-promoting signals.

Question 2

How do cancer cells evade growth suppressors?

Answer 2

Cancer cells evade growth suppressors by disrupting tumor suppressor genes, particularly RB and TP53.

Question 3

What mechanisms do cancer cells use to resist cell death?

Answer 3

Cancer cells evolve strategies to limit apoptosis, such as loss of TP53 function.

Question 4

What is the significance of enabling replicative immortality?

Answer 4

Cancer cells require unlimited replicative potential to form macroscopic tumors, often utilizing telomerase to counteract telomere shortening.

Question 5

What are enabling characteristics of cancer?

Answer 5

Enabling characteristics include genome instability and tumor-promoting inflammation, which facilitate the acquisition of hallmarks.

Question 6

What is the emerging hallmark of reprogramming energy metabolism?

Answer 6

Cancer cells often reprogram glucose metabolism to favor glycolysis, termed ‘aerobic glycolysis,’ to support their growth.

Question 7

How do tumors evade immune destruction?

Answer 7

Tumors evade immune destruction by avoiding detection or limiting the immune response, often through immunosuppressive factors.

Question 8

What is the function of pericytes in tumors?

Answer 8

Pericytes support the tumor endothelium and their absence can lead to increased cancer cell intravasation.

Question 9

What are cancer-associated fibroblasts?

Answer 9

Cancer-associated fibroblasts enhance tumor phenotypes, including proliferation and invasion, and are a major component of the tumor stroma.

Question 10

What is therapeutic targeting in cancer treatment?

Answer 10

Therapeutic targeting involves developing drugs that specifically target the molecular mechanisms underlying hallmark capabilities.

Question 11

What are the six core hallmarks of cancer?

Answer 11

• Sustaining proliferative signaling
• Evading growth suppressors
• Resisting cell death
• Enabling replicative immortality
• Inducing angiogenesis
• Activating invasion and metastasis

Hallmarks are biological capabilities acquired during tumor development, as established in the 2000 seminal paper by Hanahan and Weinberg.

Question 12

What are the two emerging hallmarks of cancer?

Answer 12

• Reprogramming energy metabolism
• Evading immune destruction

These emerging hallmarks expand the understanding of cancer biology beyond the original six hallmarks.

Question 13

How do the two new hallmarks differ from the original six?

Answer 13

The two new hallmarks incorporate aspects of the tumor’s interaction with systemic physiology, focusing on metabolism and immune evasion rather than just cell-autonomous traits

They reflect a more integrated view of tumor biology.

Question 14

What role does the tumor microenvironment play in cancer progression?

Answer 14

The tumor microenvironment supports tumor growth, progression, and metastasis through reciprocal heterotypic signaling interactions among cancer cells and stromal cells

It is essential for understanding tumor biology as it resembles an organ-like structure.

Question 15

What is the impact of reciprocal signaling in the tumor microenvironment?

Answer 15

Reciprocal signaling helps orchestrate supportive conditions for tumor growth and is essential for multistep tumor progression

Cancer cells and stromal cells continuously communicate to favor tumor development.

Question 16

What is the significance of the tumor microenvironment in metastasis?

Answer 16

The success of metastasis depends on the ability of cancer cells to re-establish supportive interactions within new tissue microenvironments or find ‘metastatic niches’

This interaction is crucial since distant organs may lack supportive stromal signals.

Question 17

What is the role of genome instability in cancer progression?

Answer 17

Genome instability leads to increased mutation rates and karyotypic instability, which are essential for acquiring hallmark capabilities

It is an enabling characteristic for cancer cell evolution.

Question 18

Define ‘aerobic glycolysis’ in the context of cancer.

Answer 18

Aerobic glycolysis is a metabolic reprogramming where cancer cells primarily rely on glycolysis for energy production, even in the presence of oxygen

This process supports the bioenergetic and biosynthetic demands of sustained proliferation.

Question 19

True or False: The tumor microenvironment consists solely of cancer cells.

Answer 19

False

The tumor microenvironment includes a diverse array of recruited normal cells.

Question 20

Fill in the blank: The process of _______ allows transformed epithelial cells to acquire the abilities to invade and disseminate.

Answer 20

epithelial-mesenchymal transition (EMT)

EMT is a critical step in the multistep process of invasion and metastasis.

Question 21

What is the function of cancer-associated fibroblasts?

Answer 21

Cancer-associated fibroblasts enhance tumor phenotypes, including cancer cell proliferation, angiogenesis, and invasion

They are often the predominant cell population in the tumor stroma.

Question 22

What is the significance of immune inflammatory cells in tumors?

Answer 22

Immune inflammatory cells contribute to tumor progression by promoting tumor growth, contrary to their expected role in tumor suppression

This includes macrophages, mast cells, and various lymphocyte subtypes.

Question 23

What is the role of endothelial cells in tumors?

Answer 23

Endothelial cells form the tumor-associated vasculature and have distinctive gene expression profiles that support tumor growth

They are essential for providing nutrients and oxygen to tumors.

Question 24

What is the impact of therapeutic targeting on cancer treatment?

Answer 24

Therapeutic targeting aims to treat cancers by focusing on specific molecular targets involved in hallmark capabilities

This approach has been a significant advancement in cancer therapy.

Question 25

True or False: Tumor-associated endothelial cells are identical to those in healthy tissues.

Answer 25

False ## Footnote They have distinctive gene expression profiles that differ from normal endothelial cells.

Question 26

What are cancer stem cells (CSCs)?

Answer 26

CSCs are defined by their ability to efficiently seed new tumors upon inoculation into recipient host mice ## Footnote They carry the oncogenic and tumor suppressor mutations that define cancer as a genetic disease.

Question 27

What is the objective of the VCOG Consensus Document on Tumor Response Evaluation in Dogs?

Answer 27

Establish standardized criteria for assessing response to therapy in canine solid tumors.

Question 28

What framework is the VCOG Consensus Document based on?

Answer 28

It is based on human RECIST v1.1 guidelines.

Question 29

What are the key recommendations for tumor response evaluation?

Answer 29

Accurate measurement of tumors in metric notation, use of imaging techniques for assessment, and classification of responses: Complete Response (CR), Partial Response (PR), Progressive Disease (PD), and Stable Disease (SD).

Question 30

Why is the VCOG Consensus Document important?

Answer 30

It facilitates comparison of treatment protocols and enhances clinical trial consistency in veterinary oncology.

Question 31

What is the maximum number of target lesions that can be chosen for assessment?

Answer 31

A maximum of five target lesions can be chosen for assessment, with a maximum of two lesions per organ.

Question 32

How should target and non-target lesions be documented in clinical trials?

Answer 32

Target lesions should be measured and followed for assessment of tumor response, while non-target lesions should be documented as 'present' or 'absent' at follow-up time points.

Question 33

What is the minimum size for tumor lesions to be measured?

Answer 33

The minimum size for tumor lesions to be measured is 10 mm for clinical examination and imaging techniques (CT, MRI), and 20 mm for thoracic radiographs.

Question 34

What are the definitions of complete response (CR), partial response (PR), and progressive disease (PD)?

Answer 34

Complete Response (CR): Disappearance of all target lesions and pathologic lymph nodes (LNs) <10 mm in short axis. Partial Response (PR): At least a 30% reduction in the sum of diameters of target lesions, referencing the baseline sum. Progressive Disease (PD): Either the appearance of one or more new lesions or at least a 20% increase in the sum of diameters of target lesions.

Question 35

What is the process for determining the best overall response in a study?

Answer 35

The best overall response is determined by assessing the best response recorded from the start of study treatment until the end of the study.

Question 36

How is the duration of overall response measured in tumor assessments?

Answer 36

The duration of Complete Response (CR) is measured from the time criteria for CR are first met until the date of recurrence is noted.

Question 37

What are the criteria for measuring target lesions in a clinical trial?

Answer 37

Target lesions must be accurately measured in at least one dimension, with the longest diameter recorded. A maximum of five target lesions should be chosen, with no more than two lesions per organ, and they must be at least 10 mm in size.

Question 38

What are the criteria for selecting target lesions in tumor assessments?

Answer 38

Target lesions should be selected based on the following criteria: they must be measurable, with a minimum size of 10 mm, and a maximum of five target lesions can be chosen, with no more than two lesions per organ.

Question 39

What is the objective of the VCOG Consensus Document on Lymphoma in Dogs?

Answer 39

The objective is to establish standardized response evaluation criteria for peripheral nodal lymphoma in dogs.

Question 40

Why is uniform assessment important in lymphoma treatment?

Answer 40

Lack of uniform assessment complicates treatment comparisons.

Question 41

What is the minimum measurable lymph node size for lymphoma assessment?

Answer 41

The minimum measurable lymph node size is set at 10 mm.

Question 42

What is the size requirement for target lesions in lymphoma treatment?

Answer 42

Target lesions must be ≥20 mm for reliable assessment.

Question 43

What are the response definitions used in lymphoma treatment?

Answer 43

The response definitions include complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).

Question 44

How often should evaluations be conducted during lymphoma treatment?

Answer 44

Standardized evaluations are recommended every month for 1.5 years, then every two months.

Question 45

What is the minimum size for a new lesion to be considered in peripheral nodal lymphoma?

Answer 45

The minimum size for a new lesion is greater than 15 mm in its longest diameter (LD).

Question 46

How are target lesions defined in lymphoma treatment for dogs?

Answer 46

Target lesions are defined as measurable lesions that must be at least 20 mm in size at baseline.

Question 47

How is disease progression determined in lymphoma treatment?

Answer 47

Disease progression is determined by the appearance of new malignant lesions classified as progressive disease (PD).

Question 48

What criteria must a new lesion meet to be considered new in disease progression?

Answer 48

A new lesion must be unequivocal, not attributable to imaging differences, and greater than 15 mm in LD.

Question 49

What methods are recommended for measuring peripheral lymph nodes in dogs?

Answer 49

Recommended methods include clinical examination and caliper measurement of enlarged lymph nodes.

Question 50

What should be done if two evaluators' measurements diverge by greater than 20%?

Answer 50

Remeasurement is required, and the mean of the resulting measurements should be used for assessment.

Question 51

What criteria are used to identify new radiographic lesions in veterinary oncology?

Answer 51

New lesions must be unequivocal, not attributable to imaging differences, and greater than 15 mm in size.

Question 52

What is the significance of a new lesion in an anatomical location not imaged at baseline?

Answer 52

It is automatically classified as a new lesion, indicating disease progression.

Question 53

What are the response evaluation criteria for peripheral nodal lymphoma in dogs?

Answer 53

Criteria include: 1. Complete Response (CR): Disappearance of all evidence of disease. 2. Partial Response (PR): At least a 30% decrease in Mean Sum LD. 3. Progressive Disease (PD): At least a 20% increase in Mean Sum LD.

Question 54

What are the limitations in measuring lymph node size in veterinary oncology?

Answer 54

Limitations include variation in body size among breeds, non-reproducible measurement techniques, and lack of standardized guidelines.