Neoplasia Flashcards
properties of a cancer cell
a. Defect in proliferation
b. Evading apoptosis
c. Angiogenesis
d. Invasion (invade local tissue)
e. Metastasis
benign tumours
grow slowly and locally, well-defined capsule, not invasive and does not metastasize, well-differentiated (resembles normal cells)
malignant tumours
grow rapidly, invades neighbouring tissues and enters blood vessels, poorly differentiated and spread distantly
carcinoma in situ (CIS)
neoplasm, lesions with all histological characteristics of cancer, but has not begun to invade local tissue
Name 3 angiogenic growth factors secreted by cancers causing angiogenesis
a. vascular endothelial GF
b. platelet derived GF
c. basic fibroblast GF
what are the most common sites of metastases?
bone, brain, lungs and liver
Two types of genes that can be affected by mutation are:
- proto-oncogenes - promotes growth
= mutation turns them into tumour inducing genes - tumour suppressor genes (BRCA 1 and 2) - suppresses tumour growth
= mutation render them inactive
carcinoma
Epithelial tissue (mucous membrane of respiratory tract, GI and GU tracts)
adenocarcinoma
From ductal or glandular tissue (skin, glands)
sarcoma
Mesenchymal tissue (connective tissue, muscle, bone and fat)
lymphoma
Lymphatic tissue, the glands of the lymphatic system
leukemia
Blood-forming cells, cancers of the bone marrow
Classification of Cancer by Grading
determined by how closely cells resemble tissue of origin
Grade I - IV
Classification of cancer by Staging
based on presence of metastasis
Stage I - IV
Clinical manifestations of Cancer
Pain Fatigue Cancer cachexia Anemia Leukopenia Thrombocytopenia GI manifestations (ulcers, malabsorption, diarrhea, nausea) Alopecia and skin breakdown
Causes of cancer include
environmental and lifestyle factors
genetic and epigenetic factors
Known risk factors of cancer
- tobacco use
- infectious agents
- lifestyle (body weight, exercise, diet and alcohol)
- UV radiation
- reproductive and hormonal factors
- environmental and occupational exposures (radiation, pollutant, chemicals)
Types of Lung Cancer
- Non small cell lung cancer
a. squamous cell carcinoma
b. adenocarcinoma
c. large cell undifferentiated carcinoma - small cell lung cancer
What is the prevalence of each type of lung cancer/
30% squamous cell
40% adenocarcinoma
10% large cell undifferentiated
20% small cell lung cancer
Squamous cell carcinoma
- associated with cigarette smoking
- not strong tendency to metastasize
- often bound in cells that line main airway - bronchi
Adenocarcinoma
- associated with scarring and fibrosis
- starts in mucous-producing cells
- most common type found in nonsmokers
Large cell undifferentiated carcinoma
- correlation with cigarette smoking and environmental carcinogens
- highly metastatic via lymphatics
Small cell lung cancer
- associated with cigarette smoking and environmental carcinogens
- most aggressive form of lung cancer
- spreads easily and often metastasize by diagnosis
- paraneoplastic syndrome
How is SCLC staged?
Limited stage - only found on one side of the chest, may include lymph nodes on same side as tumour
Extensive stage - tumour is found widely spread within the lung with the tumour to the other lung, lymph nodes on opposite side of chest and other parts of the body
Paraneoplastic syndrome
- results from hormone or cytokine release by tumour
- linked with development of SIADH, where increased ADH leads to reabsorption in collective ducts
- dilutional hyponatremia
Genes associated with lung cancer
Epidermal growth factor receptors (EGFR)
BRAF and ROS-1
Clinical manifestations of lung cancer
a. Persistent cough (key finding in most lung cancer diagnoses)
b. Sputum (possibly blood tinged)
c. Chest pain
d. Dyspnea and possibly wheezes
e. late symptoms: anorexia, fatigue, n/v, weight loss, palpable nodes
Diagnostic Studies for lung cancer
- chest x-ray
- CT scan
- sputum samples
- bronchoscopy
- biopsy
Which types of lung cancer often involve surgical resection as treatment?
Adenocarcinoma
Squamous cell carcinoma
growth fraction
percentage of actively dividing cells compared to cells in resting phase i.e. ratio of proliferating cells to G0 cells
Early stages of tumour growth
- Exponential growth, short (constant) doubling time
- Large % of actively dividing cells because of good supply of O2 and nutrients - high growth fraction
Later stages of tumour growth
- Doubling time is slowed
- Decreased growth fraction as tumour outgrows blood and nutrient supply
Transcoelomic spread
Spread of a malignancy into body cavities via penetrating the surface of the peritoneal, pleural, pericardial or subarachnoid spaces
clinically detectable tumour
10^9 (1 billion) cells = 1 g mass = 1 cm diameter
lethal tumour
10^12 (1 trillion) cells = 1 kg mass
3 consequences of late detection
- metastases likely to have formed
- tumour less responsive to therapy
- patient debilitated by disease and less tolerable to treatment
Goals of chemotherapy
a. cure
b. control
c. palliation
Factorings affecting response to cancer treatment
- tumour burden
- use of combination chemo
- administration schedule (cell cycle non/specific)
- hormone receptor status
- dose category
- supportive therapies and hematopoietic growth factors
Examples of cell cycle specific cytotoxic agents
a. antimetabolites
b. mitotic inhibitors
c. topoisomerase inhibitors
d. hypomethylating agents
Examples of cell cycle nonspecific cytotoxic agents
a. alkylating agents
b. platinum compounds
c. antitumour antibiotics
Medications that target the S-phase of the cell cycle
most antimetabolites (methotrexate, fluorouracil)
topoisomerase inhibitors (irinotecan, etoposide)
Which medication is important to give with leucovorin?
methotrexate
Which hormone antagonist should be prescribed only in post-menopausal women and why?
anastrozole
- drug blocks enzyme called aromatase, which inhibits conversion of adrenal androgens to estrogen - premenopausal women continue to produce estrogen
What is the role of corticosteroids in cancer treatment?
- antiemetic
- prevention of hypersensitivity reactions
- prevention of edema
- oncologic emergencies
- cerebral edema
When are targeted therapies used?
when tumour expresses target molecule so that drug can bind with specific cellular molecular target to exert anti-cancer effect
- blocks cell signalling
- make malignant cells more visible to immune system
What are some common side effects of cytotoxic agents?
- hematologic toxicity (neutropenia, febrile neutropenia, anemia, thrombocytopenia)
- chemotherapy induced nausea and vomiting
- mucositis
- diarrhea and constipation
- alopecia
- reproductive toxicity
Management of Neutropenia
prophylactic antibiotics and/or filgrastim
Management of Febrile Neutropenia
- hospital admission for broad spectrum IV antibiotics
- may decrease doses of chemo
- may use filgrastim
filgrastim
stimulates production and release of neutrophils from bone marrow
side effect: bone pain
Management of Anema
- rest, conserve energy
- oxygen therapy
- diet, iron supplement
- RBC transfusion
- epoetin alpha
Epoetin alpha (Eprex)
stimulates bone marrow to produce RBCs
side effect: hypertension
Management of Thrombocytopenia
a. platelet transfusion
c. avoid drugs with antiplatelet activity
d. watch for symptoms of occult bleeding
e. ensure platelet count >100/mm3 before next chemo cycle
How is the chemoreceptor trigger zone (CTZ) activated?
- vagus nerve - signals from stomach/intestine
2. emetogenic compounds that reach CTZ via bloodstream
Receptors involved in vomiting response
- serotonin
- neurokinin-1
- dopamine
- acetylcholine
- histamine
Acute CINV is associated with which chemical?
serotonin (5HT3)
Management of Mucositis
- good oral hygiene
- avoid irritating substance and smoking
- benzydamine (oral analgesic)
- systemic antibiotics
Managment of diarrhea
- replace fluid/electrolytes
- antidiarrheal (loperamide)
Management of Constipation
- dietary
- laxatives
- stool softeners
Which drug causes hand-and-foot syndrome as a unique side effect?
fluorouracil (5-FU) and capecitabine (Xeloda)
What main side effect does vincristine cause?
neurotoxicity
Which drug causes hypersensitivity reaction?
taxanes
paclitaxel (taxol)
Which drug causes severe diarrhea?
irinotecan (camptosar)
topoisomerase I inhibitor
Which drug causes hemorrhagic cystitis (bladder injury)?
cyclophosphamide
alkylating agent
Which drug causes nephrotoxicity?
cisplatin
Which drug can cause cardiotoxicity?
doxorubicin
anthracycline (antitumour antibiotic)
Which drug can cause pneumonitis and pulmonary fibrosis?
bleomycin
non-anthracyclines (antitumour antibiotic)
