(SYNOPTIC) Cancer Metastases Flashcards
What is a metastasis?
Secondary involvement of cancer spreading across the body
Cells within metastases resemble the 1y tumour
What are the main routes of metastatic spread?
(1) Lymphatic system
(2) Haematogenous spread
- via blood
(3) Transcoelomic
- through body walls into abdominal/ chest cavities
What is the process of carbohydrate interactions in disease pathways of metastatic cancers?
(1) Leukocyte captures chemo-attractants
(2) Leukocyte rolls
(3) Rolling slows
(4) Leukocyte adhesion to endothelium
(5) Transmigration + release of chemo-attractants into tissue
What is lymphatic spread?
Follows lymphatic system
Lymphadenopathy
What is lymphadenopathy?
Spread + growth of cancer cells/ reactive hyperplasia
What is haematagenous spread?
Spread of metastases via circulatory system
Veins more readily invaded than arteries
What will a cancer metastases invasion of the inferior vena cava likely cause?
Lung metastases
What is transcoelomic spread?
Spread of metastases across peritoneal cavity
Often associate with fluid buildup
Name two types of cancer metastases that have arisen from transcoelomic spread?
(1) Ovarian cancer - across peritoneum
(2) Lung cancer - across pleural cavity
State the likely location of cancer metastases based on the location of the primary cancer.
Bladder
- Bone
- Liver
- Lung
State the likely location of cancer metastases based on the location of the primary cancer.
Breast
- Bone
- Brain
- Liver
- Lung
State the likely location of cancer metastases based on the location of the primary cancer.
Colon
- Liver
- Lung
- Peritoneum
State the likely location of cancer metastases based on the location of the primary cancer.
Kidney
- Adrenal gland
- Bone
- Brain
- Liver
- Lung
State the likely location of cancer metastases based on the location of the primary cancer.
Lung
- Adrenal gland
- Bone
- Brain
- Liver
- Other lung
State the likely location of cancer metastases based on the location of the primary cancer.
Melanoma (skin)
- Bone
- Brain
- Liver
- Lung
- Skin
- Muscle
State the likely location of cancer metastases based on the location of the primary cancer.
Ovary
- Liver
- Lung
- Peritoneum
State the likely location of cancer metastases based on the location of the primary cancer.
Prostate
- Adrenal gland
- Liver
- Bone
- Lung
How are metastases diagnosed?
- CT Scans
- X-ray
- Tumour markers
- Biopsy
- Cytology
What is the pharmacological symptomatic treatment of bone metastases?
Bisphosphonates
To reduce calcium
As bone metastases are often linked to hypercalcaemia
How is spinal cord compression, due to bone metastases, treated?
Dexamethasone with PPI cover
Radiotherapy to bone
Pain relief + laxatives
What is the pharmacological treatment of brain metastases?
Dexamethasone + PPI
Often causes seizures - anti-epileptics
What is the pharmacological treatment of lung metastases?
Dexamethasone + PPI
Salbutamol to open airways (if required)
May require tranexamic acid to reduce bleeding
What is the pharmacological treatment of liver metastases for symptomatic relief?
Dexamethasone
- useful for pain
Drain ascites
What is primary chemotherapy resistance?
Intrinsic resistance to chemotherapy, regardless of drug exposure
What is acquired chemotherapy resistance?
Natural selection of tumour cells that are sensitive to chemotherapy drug die, but this does not affect the tumour as a whole
What are some mechanisms of metastases resistance?
- efficient repair to damaged DNA
- decreased intracellular activation
- increased intracellular breakdown
- bypass biochemical pathways
- overproduction of blocked enzyme
- changes to receptor
What is a cellular mechanism of defence, of a cancer cell, to alkylating agents?
Efficient repair to damaged DNA
What is a cellular mechanism of defence, of a cancer cell, to methotrexate?
(1) Decreased uptake by cell
(2) Bypass biochemical pathways
(3) Gene amplification/ overproduction of blocked enzyme
What is a cellular mechanism of defence, of a cancer cell, to doxorubicin?
Decreased uptake by cell
What is a cellular mechanism of defence, of a cancer cell, to vinca alkaloids?
Increased drug efflux
What is a cellular mechanism of defence, of a cancer cell, to anthracyclines?
Increased drug efflux
What is a cellular mechanism of defence, of a cancer cell, to 5-fluorouracil?
Decreased intracellular activation
What is a cellular mechanism of defence, of a cancer cell, to cytarabine?
Increased intracellular breakdown
What is an oncogene?
Gene that gains function when mutated
What is a tumour suppression gene?
Gene that loses function when mutated
What is EGFR, with regard to cancer?
Oncogene
What does mutated EGFR do, with regard to cancer?
Promotion of angiogenesis
What is p53?
Tumour suppressor gene
Mutated p53 suppresses apoptosis
What is PGP?
p-glycoprotein
Increases drug efflux from a cell
What does upregulation of MDR1 gene do?
Codes for PGP
Indirectly increases drug efflux from a cell
What is the MoA of cisplatin?
Forms crosslinks with purine bases on DNA
Interferes with DNA repair mechanisms
Induces apoptosis
Which receptor influences cisplatin uptake in a cell?
CTR1
What is 5-fluorouracil?
Antimetabolite chemotherapy drug
Metabolites inhibit thymidylate synthetase
- stops DNA synthesis
How does resistance to 5-fluorouracil occur?
Decreased intracellular activation of 5-FU to active metabolite
What does methotrexate inhibit?
DHFR
What effect is an overexpression of DHFR likely to have on methotrexate efficacy?
Cancer cell resistance to methotrexate
With regard to chemotherapy, what is FEC?
3 complementary chemotherapy drugs
F - Fluorouracil
- inhibits thymidylate synthetase
- stops DNA synthesis
E - Epirubicin
- forms a complex with DNA
C - Cyclophosphamide
- forms DNA + RNA crosslinks
