3.2 - Biology of Cancer Flashcards
What is Cancer
- cells divide uncontrollably and invade other tissues
Benign VS. Malignant Tumour
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
Types of Benign Tumours
1) Lipoma - fatty tissues
2) Leiomyoma - arises in smooth muscle tissue
3) Meningioma - arises from meninges
Types of Malignant Tumours
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
Carcinoma In Situ
- 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)
Characteristics of Cancer Cells
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
Proto-Oncogenes VS. Oncogenes and Tumour-Suppressor Genes
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
How are oncogenes activated
- 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
Types of Translocation that Sustain Proliferative Signalling
1) Burkitt Lymphoma
2) Chronic Myeloid Leukemia
3) Gene Amplification
gggg
What is Genomic Instability
- 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)
Telomeres
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
What is Angiogenesis
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
How cancer cells support their own growth
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
Resisting Apoptosis
- 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
Inflammation and Cancer
- 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
What is a Tumour-Associated Macrophage
- 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
Which 2 conditions cause immunosuppression which can cause cancer?
1) Non-Hodgkins lymphoma
2) Kaposi Sarcoma
Viruses that can cause cancer
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
What is Metastasis?
- 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
What is the Epithelial-Mesenchymal Transition
- 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
How does release of lytic enzymes contribute to cancer spread
- lytic enzyme release breaks down the extracellular matrix and decreases cell adhesion
- cells can break off from primary tumour and migrate to distant sites
What are paraneoplastic Syndromes?
- 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
Clinical Manifestations of Tumours
- 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
Other Clinical Manifestations
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
Stages of Cancer
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
TNM System
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
What are Tumour Markers
- 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
What is the problem with tumour markers?
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
What is an Immunohistochemical analysis?
- staining a tissue sample with antibodies that bind to specific proteins
- identifies presence and quantity of proteins in cancer cells
How does radiation work?
- kills cancer cells DNA
- minimizes damage to surrounding tissue bec it is more targeted
How does chemotherapy work?
- targets rapidly dividing cells (but healthy cells can also be rapidly dividing)
- interferes with processes that a cell requires for growth and survival
Types of Chemo
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
What is targeted disruption cancer treatment?
- aims to interfere with pathways crucial to cell growth and survival
Mechanisms:
- inactivating oncogenes
- blocking angiogenesis
- inducing apoptosis
- neutralizing cytokines
