Cancer Flashcards
Cancer characterised by?
- Loss of growth control leading to an unregulated increase in cell number
- Metastasis and invasion of other tissues
Cancer is caused by what?
Mutations in genes controlling cell growth after exposure to carcinogens
Cancer differ in what?
- Tissue of origin
- Causal factor(s)
- Molecular mechanisms
What is cancer incidence in NZ and worldwide?
Leading cause of death in NZ and second worldwide
How do tumours develop?
- Cells lose growth control causing them to proliferate and form new growth - neoplasia
- Cells do not die via apoptosis
Difference between benign and malignant tumours?
- Tumour is benign if the neoplastic cells are clustered in a single mass
- Tumour becomes malignant once cells have undergone metastasis
Characteristics of benign tumour?
- Cells are well differentiated and look like normal cells
- May perform the normal function of the tissue
e. g. secrete hormones, although may over-secrete - insulinoma - Cells grow relatively slowly but this is not suppressed by apoptosis or contact inhibition
- Size may be limited to just a few mm by lack of blood supply Surrounded by a fibrous capsule & confined to original location
- Do not infiltrate, invade, or metastasize
- Can damage nearby organs by compressing them
Characteristics of of malignant tumour?
- Cells are less differentiated and do not look like normal cells
- Do not perform the normal function of the tissue -May secrete new signalling molecules, enzymes or toxins etc.
- Cells grow rapidly since they have lost the ability to control proliferation and differentiation
- No fibrous capsule
- Cells infiltrate & invade surrounding tissues and metastasize to form new tumours at distant sites
- Tumour sends “legs” into surrounding tissue
- Can compress and/or destroy surrounding tissues
How are tumours classified?
According to tissue of origin
How are benign tumours named by?
Tissue name + -oma
How are malignant tumours names derived?
- Carcinomas are derived from epithelial cells
- Adenocarcinomas are derived from glandular epithelial cells
- Sarcomas are derived from mesenchymal cells
- Leukaemias are derived from haemopoietic cells
What is the most common type of cancer?
Carcinomas
What are examples of Adenocarcinomas?
Lung, colon, breast, pancreas, stomach, oesophagus, prostate, ovary
What are examples of Squamous cell carcinoma?
Skin, oropharynx, larynx, lung, oesophagus, cervix
What are examples of other types of carcinomas?
Small-cell lung-, large- cell lung-, haptic-, renal- and bladder- carcinomas
What are some examples of Sarcomas & Leukaemias?
Osteosarcomas (from bone), Liposarcoma (from adipose tissue), Rhabdomyosarcoma (from muscle), Acute Lymphotic Leukaemia, Acute Myelogenous Leukaemia, Multiple Myeloma
How are most adult cells characterised?
Terminally differentiated and quiescent (non-dividing)
exceptions include; hair follicles, blood and gut stem cells
How are cell numbers remained constant?
Within each tissue, cell death, by apoptosis or necrosis, is balanced by cell division, often of stem cells.
How is cell division regulated?
By growth factors which allow quiescent cells to enter the cell cycle and divide.
What are the Hallmarks of Cancer
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signals
- Evading apoptosis
- Sustained angiogenesis
- Limitless replicative potential
- Tissue invasion and metastasis
How does telomere length control lifespan?
- Cells contain telomerase, an enzyme which can elongate telomeres
- Telomerase activity is essential for allowing cells to keep proliferating
- As cells age, telomerase becomes inactive and hence telomeres shorten & cells lose the ability to divide – limits lifespan
How does increased telomerase affect cells?
Increased telomerase activity allows cells to proliferate indefinitely and leads to cancer
What is the normal cell cycle?
There are four phases:
- G1 – gap between M & S phase
- S phase – DNA synthesis/replication
- G2 – gap between S & M phase
- M phase – mitosis, cytokinesis/division
Why does the cell cycle prevent uncontrolled cell proliferation?
The cell cycle regulates cell proliferation.
If differentiated cells start dividing again or cycling cells lose control then this can lead to uncontrolled proliferation & cancer.
What are the cell cycle checkpoints?
1) G1/S transition checkpoint
- Are growth factors present?
- Are nutrients available?
- Is DNA damaged?
- Is the cell big enough?
2) G2/M transition checkpoint
- Has DNA replicated?
- Is DNA damaged?
What happens if these needs are not met?
Cell cycle arrest which can lead to cell death by apoptosis.
What are the tumour suppressors and what do they do?
p53, p21 & p27
They inhibit cell division.
What active complex is needed to pass through G1/S checkpoint?
Cdk4/6-cyclinD
What happens when DNA repair genes are mutated?
Genome instability and increased likelihood of further mutation.
What are some germline mutations?
- Rb – retinoblastoma
- BRCA1/2 – breast cancer
How many mutations are need for cancer to develop? In particular colon and lung?
2-20
Colon - 4-5
Lung - 10-15
How is it beneficial to identify molecular fingerprints of cancers?
- Screening
- Diagnosis and targeted treatments
- Understanding mechanism and development of new therapies
What are the two main mutations types affecting cell proliferation?
- Oncogenes
- Tumour suppressor genes
What are proto-oncogenes and how do oncogenes vary?
Proto-oncogenes normally stimulate cell proliferation allowing progression from G1 to S phase. Oncogenes are mutations that allow this progression in the absence of growth factors.
What are TSGs and how do mutations of these cause cancer?
Tumour suppressor genes negatively regulate cell division, preventing
abnormal proliferation, suppressing tumorigenesis.
Mutations cause a loss of function, allowing DNA that is damager or not fully replicated to progress through cell cycle.
What is the Ras-MAPK pathway and how do mutations affect it?
Growth factors activate the pathway, activating Cdk4/6 and allows progression through the G1/S checkpoint and cell division. Activating mutations enable the pathway to always be active, enabling cell division independently of growth factors (oncogene).
What is p53 and how do mutations affect it?
p53 senses DNA damage.
Inactivating mutations of p53 disables its ability to cause cell apoptosis when damage has occurred.
What are the stages of cancer development?
1) Initiation
- Exposure to carcinogen
- Damage to DNA
2) Promotion
- Altered cell divide via tumour promoter
- Altered cells remain dormant or removed
3) Progression
- More mutations
- Uncontrolled cell replication and loss of specialisation
- Cells are aggressive and invasive
What is intravasation?
The ability for cells in primary tumour to escape into the circulation
- Loss of adhesion
- Secretion of proteases to degrade basement membrane
How does cancer complete invasion and metastasis?
Cells develop intravasation, survive in blood or lymphatic system, complete extravasation, develop into secondary tumour, angiogenesis, metastasis of multiple distant sites
What are host risk factors?
- Hereditary
- Reproductive hormones - can act as tumour promoters
- Obesity - insulin promotes tumour growth
Immune surveillance of tumour antigens
What are environmental risk factors?
- Chemical carcinogens (Smoking, alcohol, occupational exposure)
- Viruses and bacteria (Hepatitis, HPV)
- Radiation (UV exposure, radioactivity)
Benefits of fruit and vegetables?
May protect by blocking effects of carcinogens or suppressing growth of tumour cells.
What are some local effect - clinical manifestations from tumours?
- Compression or blockage of structures close by
- Blood vessels - bleeding or blockage
- Effusions - build up of fluid (pleural effusion, ascites)
What are some systemic effect - clinical manifestations from tumours?
- Malnutrition (Malabsorption, anaemia, anorexia & Cachexia)
- Fluid and electrolyte imbalances
- Fatigue and sleep disturbances
- Paraneoplastic syndromes
- Pain in later stages
What is anorexia-cachexia syndrome?
Protein/energy malnutrition due to:
- Increased energy demand
- Reduced energy intake & malabsorption
What are the seven warning signs of cancer
- Change in bowel or bladder habits
- A sore that does not heal
- Unusual bleeding or discharge from any body orifice
- Thickening or a lump in the breast or elsewhere
- Indigestion or difficulty swallowing
- Obvious change in a wart or mole
- Nagging cough or hoarseness
How do you screen and diagnose cancer?
- Indirect, non-specific tests (blood count, abnormal hormones)
- Cytology (pap smear, tissue biopsy)
- Diagnostic imaging (x-ray, MRO, ultrasound)
- Tumour markers (prostate-specific antigen PSA)
- Microarray technology (gene chips measure mRNAs)
What is the tumour grading?
- Grade l - Cells differ slightly from normal cells and are well differentiated
- Grade ll - Cells are more abnormal and moderately differentiated
- Grade lll - Cells are very abnormal and poorly differentiated
- Grade lV - Cells are immature and undifferentiated
What is the overall tumour staging?
- Stage 0 - Cancer in situ
- Stage l - Tumour limited to the tissue of origin
- Stage ll - Limited local spread
- Stage lll - Extensive local and regional spread
- Stage lV – Metastasis to distant sites
What is the TNM staging?
- T 1 – 4 = tumour size
- N 0 – 3 = lymph node involvement
- M 0 – 1 = metastasis
What involves prevention of cancer?
- Avoiding environmental exposure
- Diet, smoking alcohol, obesity
- Products e.g sunscreen
- Vaccination HPV
- Routine screening (Smear)
- Education
Cancer treatment?
- Surgery (if no metastasis)
- Radiation therapy (apoptosis)
- Chemotherapy (targets rapidly dividing cells)
- Hormone and anti-hormone therapy
- Immunotherapy (stimulate immune system to kill cancer cells)
- Targeted therapies
What are the most prevalent cancers in NZ?
1) Lung
2) Bowel
3) Breast
Lung cancer incidence and risk factors?
- Adults 40 - 70 yrs old
- Usually diagnosed late & after metastasis
- 80-90% due to long term exposure to carcinogens in tobacco smoke
- Occupational exposure
Lung cancer signs and symptoms?
- Persistent, worsening cough
- Coughing up excessive phlegm with blood
- Chest pain with coughing or breathing
- Recurring chest infections
Lung cancer diagnosis?
- Symptoms
- Chest x-ray, CT scan
- Sputum cytology
Lung cancer prevention & treatment?
- Cessation of smoking
- Surgery
- Radiation
- Chemotherapy
Bowel cancer incidence and risk factors?
- Adults 50+ yrs old, slightly more prevalent in men
- Early detection and treatment gives 90% chance of long term survival
- Increasing age & low fibre, high fat diet
- Inflammatory bowel
- Hereditary nonpolyposis colorectal cancer
Bowel cancer signs and symptoms?
- Blood in bowel motions or change in bowel habits for several weeks
- Abdominal discomfort e.g. bloating, cramps etc
- Unexplained weight loss, tiredness, anaemia
What is the multistep progression of bowel cancer?
1) Normal colon epithelium
2) Hyper proliferating epithelium
3) Benign adenoma (polyp)
4) Intermediate adenoma
5) Late adenoma with villi
6) Adeno- carcinoma
7) Metastatic colon cancer
Bowel cancer diagnosis?
- Rectal and abdominal exam
- Blood tests
- Colonoscopy; CT colonography
Bowel cancer prevention?
- Maintain a healthy diet & weight
- Regular exercise
- Quit smoking & cut back on alcohol
- Bowel screening helps earlier detection
Bowel cancer treatment?
- Surgery
- Radiation
- Chemotherapy
Breast cancer incidence?
- Most common cancer in women (1 in 9 will be affected)
- Most will have no family history
Breast cancer signs and symptoms?
- Change in breast shape or lumps in breast
- Thickening of tissue
- Nipple changes e.g. skin dimpling
- Blood stained discharge from nipple
- Rash
- Painful area
Breast cancer host risk factors?
- Being female
- 50+ years old
- Previously having breast cancer
- Increased number of abnormal cells in milk ducts
- Affected first degree relative (risk doubles)
- Mutation of BRCA1 (Chr 17) and BRCA2 (Chr 13) genes
Breast cancer environmental risk factors?
- Nulliparity – not having given birth
- First child after 30
- High fat diet, alcohol use
- Oestrogen replacement therapy
Breast cancer hormone & growth factor effects?
- Circulating oestrogen and progesterone (can act as tumour promoter)
- Amplification of HER2 (acts as oncogene)
Breast cancer diagnosis?
Medical history; physical exam; mammogram/ultrasound; biopsy and lab testing on tissue
Breast cancer prevention?
- Regular mammogram
- Self examination
- Good lifestyle
Breast cancer treatment?
- Surgery, radiation, chemotherapy
- Hormone treatment (block hormone receptors or lower hormone levels)
Skin cancer incidence?
NZ has highest rate in the world
Skin cancer risk factors?
- Family history
- Skin that burns easily
- Cumulative sun exposure (age) or episodes of severe sunburn, esp. as a child
- Sunbeds
Skin cancer signs and symptoms?
Red, scaly, rough skin lesions on sun-exposed areas; hands, head, neck, lips and ears
Skin cancer diagnosis?
- Skin checks, mole maps
- Biopsy
Skin cancer prevention?
- Cover skin
- Check skin
Skin cancer treatment?
- Surgery
- Radiation
- Photodynamic therapy - photosensitiser drug and light or laser treatment kills tumour cells with reactive oxygen species (ROS)
Prostate cancer incidence and risk factors?
- Second most frequently diagnosed cancer
- Male > 50 yrs
- Poor diet – obesity, link with red meat?
- Family history, BRCA1/2
- Elevated testosterone
Prostate cancer signs and symptoms?
- Initially asymptomatic
- Frequent urination, pain or difficulty with urination, blood in urine
Prostate cancer diagnosis?
- Digital rectal examination (DRE), ultrasound, MRI, biopsy
- Screening for prostate-specific antigen (PSA) useful
Prostate cancer prevention?
Diet/exercise?
Prostate cancer treatment?
- Most are slow growing - managed with drugs to ↓ testosterone (Finasteride)
- For aggressive tumours - surgery, radiation / brachytherapy, chemotherapy
Cervical cancer incidence?
4th most common cancer in women worldwide
Cervical cancer risk factors?
- HPV greatest risk factor (mostly subtypes 16 & 18)
- Number of sexual partners
- Family history, smoking, poor diet
Cervical cancer signs and symptoms?
- Abnormal vaginal bleeding or discharge
- Tiredness, pain in pelvic area, legs or lower back
Cervical cancer prevention?
- Cervical screening using Papanicolaou (Pap) or smear test – every 3 years
- HPV vaccination
- Barrier protection during intercourse
Cervical cancer diagnosis?
- Pap test, visual inspection (colposcopy), and biopsy
- Also imaging (ultrasound, CT, MRI, PET, bone scan)
Cervical cancer treatment?
Surgery, radiation / brachytherapy, chemotherapy
