Cancer Mechanism Of Resistance and Development of Metastases Flashcards
How does cancer normally spread?
- Local invasion- infiltrate, invade and destroy surrounding tissue
- Example: colorectal cancer perforates colon wall, ovarian cancer grows into fallopian tubes (not metastatic cancer)
What is metastasis
When the primary cancer spreads to other cells in the body
Secondary involvement = metastases
Example: teratoma removed from the brain that normally originates from sex organs so it resembles primary malignancy
What are the steps to developing invasive cancer cells?
- Normal
Acquired DNA damage- chemicals, radiation, viruses
2. DNA damaged cell Mutations in DNA repair Genes affecting cell growth Genes regulating apoptosis Inactivation of tumour suppression gene
- Altered neoplastic cell
Expression of gene product
Loss of regulatory genes
4. Clonal expansion Self sufficiency Insensitive to growth signals Evasion of apoptosis Endless replication Neoangiogenesis EMT program activation Stomal microenvironment cross talk and release of inflammatory factors Invasive and metastatic phenotype
What are the routes for metastatic spread?
- Lymphatic spread to lymph nodes elsewhere- Lymphadenopathy
- Haematogenous spread via blood
veins are more easily invaded than arteries
portal system invasion- lung metastases
inferior vena cava (IVC)- lung metastases
crossing blood brain barrier- brain metastases - Through body walls into abdominal or chest cavities
Describe the soil and seed hypothesis?
- The tumour forms at the primary site known as the seed
2. It enters the blood stream through ‘intravasation’ and into brain parenchyma known as soil via ‘dissemination’
What is Transcoelomic spread?
Moving across the peritoneal cavity where surfaces/organs of the abdominal and pelvic cavities are covered by peritoneum
Associated with inflammatory response and fluid build up due to presence of cancer cells in cavity- ascites
Example:
Ovarian cancer goes across peritoneum leading to ascites
Lung cancer across pleural cavity leads to pleural effusion
Give examples of typical cancer spreading
Breast cancer: spreads to liver, lung, brain, bone
Lung cancer: spreads to liver, brain and adrenal gland
Melanoma: spreads to lung, liver, brain, bone, skin
How do we diagnoses metastases
Using CT scan, tumour markers, biopsy, cytology
black and white spots on imaging
What are the common complications from bone metastases and what cancers does it normally originate from
Hypercalcaemia- bisphosphonates used to reduce this
Very painful and can lead to fractures
Can cause spinal cord compression
Originates from: Radiotherapy manages symptoms
Renal
Breast
Prostate Ca
How do you treat spinal cord compression
Dexamethasone 8mg BD with PPI cover
Radiotherapy to bone
Rare to use chemo (takes too long)
Pain relief
Laxatives- common side effect is constipation as nerves to bowel/bladder often affected
How do you treat brain metastases
Dexamethasone 2-8mg OD with PPI cover
Seizure causes means anti-epileptic use
can trigger CTZ
Anti-emetics often needed
May require anxiolytics
Headaches and dizziness often occur
How do you treat lung metastases
Dexamethasone 2-8mg OD with PPI cover to limit inflammation
Salbutamol to open airways
Linked to haemoptysis- coughing up blood
May need tranexamic acid to reduce bleeding
Can cause superior vena cava obstruction (SVCO)
How do you treat superior vena cava obstruction
Dexamethasone 8mg with PPI cover
Chemotherapy especially if SCLC is very chemorpsponsive
Radiotherapy if not chemo sensitive
Stent
Pain relief
Anti-coagulants if clot expected
How do you treat liver metastases and what can it lead to
Dexamethasone 2-4mg OD useful for pain
Can lead to liver capsular pain
Jaundice + pruritus
May help with creams but anti-histamines may cause drowsiness so beware
Ascites- drainage
What is primary chemotherapy resistance
Decreased drug activity- present prior to drug exposure, tumour insensitive to initial treatment
