Lecture 8: Neoplasia II Flashcards
Examples of causes of cancer
Smoking
Diet, overweight and obesity
Lack of exercise
Viruses
Alcohol
UV and ionizing radiation
Occupational carcinogens
Smoking cessation and cancer progression
See figure
Example of cancer vaccine
HPV 6, 11, 16, and 18 associated with 70% of cervical cancers in women; also anal and mouth cancers
Nobel prize for zur Hausen in 2008
“Gardasil” is available for teen girls (prevention) but uptake is too low
Now including teen boys in Manitoba
Points for cancer control
Prevention
Early diagnosis
Therapies for primary tumor
Therapies for systemic disease (metastases)
Palliative care
Cancer diagnostic tests
Blood, urine, ascites fluid for biomarkers
Blood in urine / feces
Biopsy of tumor/lymphnodes (fine needles aspirates; multi-needle biopsy cores)
Cytology of cells scraped (eg.Papsmear)
Imaging (X-ray, MRI, PET, CT)
Palpation
Common tumour biomarkers
Ovarian cancer: CA-125
Prostate cancer: PSA
Colorectal cancer: CEA, K-ras
Breast cancer: ER, PR, HER2
Testicular cancer: AFP, hCG
How are tumour biomarkers used?
Diagnosis—to confirm the results of other tests and symptoms
Prognosis—to predict the cancer’s behavior, response to treatment, and chance of recovery
Monitor treatment—to determine how the cancer is responding to treatment
Surveillance—to determine whether the cancer has returned after treatment (relapse)
Screening—to find cancer in healthy or high-risk people before symptoms develop
What do tumour grading systems rely on?
pathologists’ assessment of:
cell differentiation
nuclear abnormality
size
shape
proportion of involvement
What is the TNM staging system?
uses information from biopsy, surgery, imaging to assign clinical stage based on usual clinical course (prognosis and therapy)
T [tumor] 1,2,3,or 4 - primary tumor site based on size,
number, location, vascular invasion
N [node] 0 or 1 - metastasis in regional lymph node
M [metastases] 0 or 1 - metastasis in distant organ / tissue
Growth factor receptors
All are cross-membrane proteins with an extracellular domain and their cytoplasmic tyrosine kinase domain in the cytosol
Cancers can overexposes these receptors and ligands
EGF receptor (cysteine rich domain)
IGF-1 receptor (has cysteine bonds in extracellular portion)
PDGF receptor
NGF receptor
FGF receptor
VEGF receptor (has Ig-like extracellular domain)
See figures
Example of nuclear hormone receptors
Half of breast cancers express Estrogen Receptor (ER)
Over 70% of prostate cancers express Androgen Receptor (AR)
Receptor antagonists in ER positive breast cancers
ER positive breast cancers can be treated with receptor antagonists (such as tamoxifen) or aromatase inhibitors (block estrogen production)
Receptor antagonists in AR positive prostate cancers
AR positive prostate cancers can be treated with receptor antagonists (such as flutamide) or GnRH agonists (block androgen production)
Bcr-Abl fusion
Philadelphia
Occurs in leukaemia cells
Part of Bcr gene from chr 22 is translocated to All gene on chr 9
creates fused Bcr/Abl gene, which is transcripts into mRNA, which is translated into protein
See figure
Example of tumour grading and staging
Gleason grade in prostate cancer is most aggressive form
Gleevac
Novel treatment
Normally, the Bcr-Abl protein requires ATP to phosphorylate its substrate protein. This phosphorylation leads to cell survival and proliferation, which leads to leukaemia.
When Gleevec is present, it binds to the ATP binding site on Bcr-Abl. The substrate protein cannot become phosphorylated.
See figure
Tumor microenvironment
Important
Can turn off immune cells, which means they cannot target the cancer cells (suppression of recognition)
See figure
Characteristics of cancer cells - signals that regulate cell proliferation
Disregard the external and internal signals that regulate cell proliferation.
Characteristics of cancer cells - apoptosis and proliferation
Avoid suicide by apoptosis (enhanced survival)
Circumvent programmed limitations to proliferation, escaping senescence and avoiding terminal differentiation.
Characteristics of cancer cells - genetic stability
Genetically unstable.
Characteristics of cancer cells - tissue homeostasis
Disregard signals for tissue homeostasis and become locally invasive
(proteolysis).
Characteristics of cancer cells - movement
Survive and proliferate in foreign sites (metastasis)
Characteristics of cancer cells - drugs
May develop capacity to pump out drugs (MDR1).
Ideally, use multiple drugs to cure cancer
See figure
Death rates for different cancers in females
Uterine cancer: has decreased in part due to PAP testes and precancerous tissue removal
Breast cancer: slight decline
Stomach cancer: decreasing, people used to eat out of cans
Lung cancer: after the war, lung cancer is up
Colorectal cancer: decreasing due to early ID and treatments
See figure
Death rates for different cancers in males
See figure
What is the most common type of lung cancer? How do lung cancers present?
Adenocarinomas
Present as cough, chest pain, weight loss (like pneumonia / bronchitis)
What is necessary for treatment of lung cancer?
TNM staging necessary for treatment decisions (resection, imaging, nodes)
How are breast cancers detected?
Detection by screening mammography or palpation
How are breast cancers treated?
Tumor resection and local lymph nodes assessed for ER, PR, HER2
Treatment plan patient-specific
How can long term survival be increased for patient with breast cancer?
by use of anti-ER (tamoxifen) and anti-HER2 (trastuzumab) when indicated
What is the most common cancer in men?
Prostate
How is prostate cancer diagnosed?
Digital rectal exam (DGE), PSA level high and increasing
Biopsies to assign Gleason score
Symptoms of prostate cancer
Often no symptoms, may not affect urinary tract
Benign prostatic hyperplasia (BPH) is not a precursor
Frequent urination occurs when there is BPH
How to stop advanced disease?
Surgery, radiation androgen ablation for advanced disease
How does colorectal cancer occur?
Polyps process to adenocarcinoma
How does colorectal cancer present?
Bloody stool
Altered bowel habits
What happens after colorectal cancer is diagnosed?
Colonoscopy and CT scan for spread
Surgical resection followed by chemo if stage III (CEA biomarker)
Novel anti-EGFR agents effective when indicated
How does cancer affect the host?
Tumor displaces/replaces/invades normal tissue (impingement, loss of function, bleeding, spinal cord compression, superior vena cava obstruction)
Ectopic production of hormones, cytokines, growth factors
Tumor creates ionic imbalances; cachexia (weight loss, muscle atrophy, lipolysis, loss of appetite)
Tumor necrosis, fever, pain
How cancer treatment affects the host?
Radiation - damage to adjacent normal tissue
Chemotherapy - damage to systemic normal tissue (hair loss, tumor lysis, nausea, peripheral neuropathy, cardiovascular damage)
