Mechanisms of invasion and metastasis Flashcards
Modes of spread
Invasion: local spread
Metastasis: lymphatic spread
Metastasis: haematogenous spread
Metastasis: transcoelomic spread
Invasion: local spread
Path of least resistance
Tissue destruction
Perineural spread
Metastasis: lymphatic vessels
Invasion of vessels: embolism or permeation
Spread to draining lymph nodes
Metastasis: haematogenous spread
Invasion - mainly veins Organs -liver -lung -bone -brain
Metastasis: transcoelomic spread
Spread across serous cavities
-e.g. abdominal cavity
Mechanisms of spread
Tumour cells interact with cells and molecules in local environment Tumour cells gain new abilities -motility is enhanced -alter adhesion molecules make poor basement membrane >protease production or reduce inhibitors -alter ECM 'Metastatic cascade'
Pathway leading to metastasis
- Primary tumour formation
- Local invasion
- Intravasation
- Survival in circulation
- Arrest at distant organ site
- Extravasation
- Micrometastasis formation
- Metastatic colonisation
- Clinically detectable macroscopic metastases
Patterns of spread
Carcinomas -lymphatic -blood (often later) Sarcomas -blood (lymphatic spread rare) Predictable patterns of spread -lung to local nodes, liver, bone and brain -tongue to neck nodes, later lung and spine
Effects of tumour spread
Pressure and obstruction Destruction Haemorrhage Infection Pain Anaemia Starvation and cachexia
Non-metastatic effects (sometimes called paraneoplastic syndrome)
Often caused by biochemical substances released by tumour cells, e.g. TNKα
- fever, anorexia and weight loss/ cachexia
- endocrine syndromes: Cushings syndrome, metabolic effects e.g. hypocalcaemia
- neurological problems e.g. neuropathy
- haematological syndromes e.g. erythrocytosis
Grading of tumours
Histological assessment
Often related to differentiation
-the more differentiated, often the less aggressive
Linked to prognosis
Various methods
-numerical grades (1, 2, 3 etc.)
-low, intermediate, high (more likely to die of a low grade tumour)
Can we predict how tumours will behave?
Grading of tumours
Staging of tumours
Staging of tumours
Clinical extent of tumour
TNM system (tumour nodes [regional] and metastases [distant])
Specific staging systems for tissue/ tumour
-lower stage means more chance of survival
Diagnosis of cancer
Biopsy [main]
Cytology (FNA)
Imaging - CT and MR scanning
Molecular analysis
Treatment
Surgery Radiotherapy Chemotherapy Biological (immune) therapy Supportive care
Oral malignancy
Need good access for safe tumour clearance
Side effects of radiotherapy
Tiredness Feeling sick Difficulty eating and drinking Skin reaction Hair loss Haematological changes Possible long-term side effects Salivary gland dysfunction --> dry mouth
Chemotherapy: types of drugs used in cancer treatment
Conventional chemotherapy agents (cytotoxic) - main
-not selective
-directly targeting DNA structure or segregation of DNA as chromosomes in mitosis
Targeted agents
Hormonal therapies
Biological therapies
-last 3 future of cancer therapy
Side effects of chemotherapy
Alopecia Mucositis Pulmonary fibrosis Cardiotoxicity Nausea/ vomiting Diarrhoea Renal failure Sterility
Targeted cancer therapies
Immune system activation (vaccines)
Growth factor receptors (oncogenes)
among many others
Cancer biomarkers: what can be answered by them?
Prognostic: is it likely to develop this cancer?
Diagnostic: what type of cancer is it?
Predictive: is this the optimal drug for my cancer?
Pharmacodynamics: what’s the optimal dose for my body?
Recurrence: will the cancer return?
Oral problems in cancer management
Dry mouth Difficulty in maintaining oral hygiene Immunocompromised -oral mucosal disease -dental disease -discomfort -social embarrassment
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