3.2 - Biology of Cancer

Question 1

What is Cancer

Answer 1

• cells divide uncontrollably and invade other tissues

Question 2

Benign VS. Malignant Tumour

Answer 2

Benign
- grows slowly
- well-defined boundary (encapsulated; so don’t invade other tissues)
- not invasive
- well-differentiated
- low mitotic index (not many cells are dividing)
- does not metastasize

Malignant
- grows rapidly
- not ecapsulated (invades)
- poorly differentiated
- high mitotic index
- metastasizes

Question 3

Types of Benign Tumours

Answer 3

1) Lipoma - fatty tissues

2) Leiomyoma - arises in smooth muscle tissue

3) Meningioma - arises from meninges

Question 4

Types of Malignant Tumours

Answer 4

1) Carcinoma - epithelial tissue
2) Adenocarcinoma - glandular/ductal tissues
3) Sarcoma - mesenchymal tissues (supports bone, muscle, and fat)
4) Lymphoma - lymphatic tissues
5) Leukemia - blood forming cells

Question 5

Carcinoma In Situ

Answer 5

• originates in epithelial or glandular tissue
• pre invasive (bc it has not yet invaded)
• cancer cells that have not yet invaded surrounding tissue (has NOT broken through basement membrane)

Question 6

Characteristics of Cancer Cells

Answer 6

1) Decreased need for growth factors
- normal cells require signals for when to grow and divide
- cancer cells just keep growing

2) Lack contact inhibition
- normal cells stop growing when they touch neighbouring cell
- cancer cells ignore this

3) Anchor dependence
- normal cells are attached to a surface
- cancer cells are not attached to anything

4) Immortality
- cancer cells can divide infinitely bc they have telomerase to maintain their chromosomes

Question 7

Proto-Oncogenes VS. Oncogenes and Tumour-Suppressor Genes

Answer 7

Proto-Oncogenes
- normal genes
- regulate cell growth and protein production
- become oncogenes, when mutated

Oncogenes
- mutant gene that causes uncontrolled proliferation

Tumour-Suppressor Genes
- aka anti-oncogene
- help control cell growth

Question 8

How are oncogenes activated

Answer 8

• RAS regulates cell growth (acts a switch that turns growth signals on/off)
• point mutation in RAS causes switch to get stuck on = uncontrolled proliferation

Question 9

Types of Translocation that Sustain Proliferative Signalling

Answer 9

1) Burkitt Lymphoma

2) Chronic Myeloid Leukemia

3) Gene Amplification

Question 10

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Question 11

What is Genomic Instability

Answer 11

• increased tendency for cells to accumulate mutations
• genetic errors can lead to activation of oncogenes or de-activation of tumour-suppressor genes

Caretaker Proteins: encodes for proteins involved in DNA repair

Chromosomal Instability - changes in chromosome # and structure
- results in chromosome loss, loss of heterozygosity (2nd copy provides protection)n
- chromosomal amplification (extra copies can lead to overexpression of oncogenes)

Question 12

Telomeres

Answer 12

telomeres: caps at the end of chromosomes
- everytime a cell divides, telomeres shrink
- when it becomes too short cell is signalled to stop dividing
- cancer cells have an enzyme - telomerase - which extends telomeres and allows cells to continue dividing

Question 13

What is Angiogenesis

Answer 13

angiogenesis: formation of new blood vessels
- they need more blood vessels to be supplied with nutrients and oxygen to continue growing
- cancers secrete angiogenic factors that support blood vessels and help endothelial cells migrate to tumour

Question 14

How cancer cells support their own growth

Answer 14

1) Warburg Effect
- cancer cells prefer to use glycolysis instead of oxygen
- cancer cells us by products of glycolysis to help them build new cell structures and continue growing
- warburg effect is driven by inactivation of tumour-suppressor genes

Reverse Warburg
- cancer cells influence surrounding cells to witch to glycolysis so they can increase their energy supply from the byproducts

Question 15

Resisting Apoptosis

Answer 15

• defects in intrinsic and extrinsic pathways provide resistance to apoptosis

Intrinsic Path
- triggered by internal signals (DNA damage)
- normally activates apoptosis
- mutations (p53) disable this pathway

Extrinsic Path
- activated by external signals from other cells or receptors
- cancer cells can block receptors from receiving apoptotic signals

Question 16

Inflammation and Cancer

Answer 16

• chronic inflammation causes release of cytokines
• cytokines promote cell growth and survival
• excessive cytokine release promote tumour growth and development

ex. H pylori can cause chronic inflammation = cancer

• H. pylori led to the discovery that antibiotics can reduce risk of cancer bc: if you remove inflammation, you stop excessive cytokine release = controlled cell growth

Question 17

What is a Tumour-Associated Macrophage

Answer 17

• key cell that promote tumour survival
• blocks t-cytotoxic cells and natural killer cells which kill abnormal cells and release cytokines which promote tumour growth and spread

Question 18

Which 2 conditions cause immunosuppression which can cause cancer?

Answer 18

1) Non-Hodgkins lymphoma
2) Kaposi Sarcoma

Question 19

Viruses that can cause cancer

Answer 19

1) Hep B and C Viruses
- cause chronic liver infection and inflammation = cancer

2) EBV
- associated w many types of cancers

3) Kaposi Sarcoma
- causes immunosuppression = cancer

4) HPV
- associated with oral, anal, and cervical cancers

5) Human T cell Lymphotrophic virus
- linked to T cell leukemia

Question 20

What is Metastasis?

Answer 20

• spread of cancer from primary site to a distant site

Occurs through 2 routes:
1) Direct Invasion
- cancer directly invades neighbouring cells

2) Metastasis to distant organs
- cancer cells travel through lymphatic system or bloodstream

Question 21

What is the Epithelial-Mesenchymal Transition

Answer 21

• process where epithelial cells transform into mesenchymal cells which is needed for metastasis

During EMT, epithelial cells
1) lose cell adhesion - allows them to be more mobile ad invasive

2) increased migratory capacity
- cells can move and spread to diff locations

3) resistant to apoptosis

4) causes stem-cell state
- less specialized
- allows them to adapt and thrive in diff environments

Question 22

How does release of lytic enzymes contribute to cancer spread

Answer 22

• lytic enzyme release breaks down the extracellular matrix and decreases cell adhesion
• cells can break off from primary tumour and migrate to distant sites

Question 23

What are paraneoplastic Syndromes?

Answer 23

• health issues triggered by substances released by the tumour
  ex. lung cancer can release hormones that affect Ca levels and cause hypercalcemia
• serves as the earliest indicator of cancer

Question 24

Clinical Manifestations of Tumours

Answer 24

• little to no pain

Mechanisms
1) pressure - tumours put pressure on tissues

2) blocks ducts - tumours can obstruct ducts = accumulation of fluid = pain

3) Invasion - can invade sensitive areas or nerve tissues

4) Stretching of surface - bc tumours keep growing

5) Tissue destruction

Question 25

Other Clinical Manifestations

Answer 25

1) Fatigue - most reported symptom 2) Cachexia - severe form of malnutrition - includes: weight loss, altered metabolism, early satiety, taste alterations, anemia 3) Anemia - decrease in hemoglobin in blood 4) Infection - when leukocyte and neutrophils counts fall, our ability to fight infections decreases 5) Leukopenia and thrombocytopenia - direct tumour invasion of bone marrow cause leukopenia (decrease in white blood cells) and thrombocytopenia (decrease in platelets) 6) GI - oral ulcers develop due to decreased cell turnover - malabsorption - treatment affects digestive systems ability to absorb nutrients - nausea - from chemo 7) Hair and skin - alopecia - from chemo - skin breakdown

Question 26

Stages of Cancer

Answer 26

Stage 1 - Early stage - no spread to lymph nodes or tissues - localized to OG site Stage 2 - Localized - starts growing into nearby tissues Stage 3 - Regional Spread - affects surrounding tissue - spreads to distant lymph nodes Stage 4 - Distant spread - cancer has spread to distant organs and tissues

Question 27

TNM System

Answer 27

T - Tumour Size T-1: 0-2 cm T-2: 3-5cm T-3: >5cm T-4: tumour has broken through skin N - Lymph Node N-0: can not feel noded N-1: swollen nodes N-2: swollen and lumpy nodes N-3: swollen nodes near collarbone M-metastasis M-0: nodes are cancer free M-1: nodes show cancer cells or metastasis

Question 28

What are Tumour Markers

Answer 28

- substances produced by cancer cells that are found on or in tumour cells, blood, CSF, or urine - help to diagnose specific types of tumours Hormones - ex. Certain breast cancer produces estrogen Enzymes -ex. Elevated levels of alkaline phosphates can be a sign of liver or bone cancer Genes (mutations) - ex. Mutations in BRCA 1 - which are linked to breast Antigens - trigger an immune response ex. Prostate specific antigen (PSA) indicates prostate cancer Antibodies - some tumours produce specific antibodies

Question 29

What is the problem with tumour markers?

Answer 29

1) False positives - tumour markers can be elevated in other cases that are not cancer ex. Elevated prostate antigen levels can occur due to benign prostate hyperplasia 2) False Negative - some cancer do not produce detectable levels of tumour markers

Question 30

What is an Immunohistochemical analysis?

Answer 30

- staining a tissue sample with antibodies that bind to specific proteins - identifies presence and quantity of proteins in cancer cells

Question 31

How does radiation work?

Answer 31

- kills cancer cells DNA - minimizes damage to surrounding tissue bec it is more targeted

Question 32

How does chemotherapy work?

Answer 32

- targets rapidly dividing cells (but healthy cells can also be rapidly dividing) - interferes with processes that a cell requires for growth and survival

Question 33

Types of Chemo

Answer 33

1) Induction - used to shrink or eliminate tumours 2) Adjuvant - given after surgery - used to kill remaining cells that may have not been removed during surgery 3) Neoadjuvant - given BEFORE surgery - tried to reduce size of the tumour; making it easier to remove in surgery

Question 34

What is targeted disruption cancer treatment?

Answer 34

- aims to interfere with pathways crucial to cell growth and survival Mechanisms: - inactivating oncogenes - blocking angiogenesis - inducing apoptosis - neutralizing cytokines