CANCER DEVELOPMENT AND THERAPEUTIC DIFFERENTIALS Flashcards
appearance of malignant cells under the microscope
- large number of irregularly shaped dividing cells
- large, variably shaped nuclei
- small cytoplasmic volume relative to nuclei
- variation in cell type and shape
- loss of normal specialised cell features
- disorganised arrangement of cells
- poorly defined tumour boundary
cell characteristics in benign tumours
similar to cell of origin (well differentiated)
cell characteristics in malignant tumours
dissimilar from cell of origin (poorly differentiated)
growth characteristics of benign tumours
tumour edges move outward in a smooth manner (encapsulated), grows by expansion and compresses and displaces surrounding tissues
tumour cells stay attached to the clone or mass of cells and do not break away and start new growths elsewhere in the body
growth characteristics in malignant tumours
the tumour edges move outward in an irregular fashion (usually no capsule) and can infiltrate, invade, and destroy surrounding tissues
tumour cells can break away from the cloned mass, live independently, move to other area of the body and start new clones or growths
rate of growth in benign tumours
slow growth rate
rate of growth in malignant tissues
rapid growth rate
degree of vascularity in benign tumours
slight vascularity
degree of vascularity in malignant tissues
moderate-marked vascularity
recurrence after surgical removal in benign tumours
seldom recurs after removal
recurrence in surgical removal in malignant tumours
frequently recurs after removal
degree of necrosis and ulceration in benign tumours
necrosis and ulceration unusual
degree of necrosis and ulceration in malignant tumours
necrosis and ulceration common
likelihood of benign tumours causing systemic effects
systemic effects are unusual unless the tumour is a secreting endocrine neoplasm
likelihood of malignant tumours causing systemic effects
systemic effects are common and usually life-threatening
what is tumour grade based on
- degree of differentiation
- spread
- size
- organisation of tumour
a feature of both benign and malignant cells
LOCAL INVASION
however all benign tumours grow as cohesive, expansive masses
invasion features in benign tumours
- benign remain localised to their site of origin
- as they grow, usually develop a rim of compressed connective tissue, a fibrous capsule that separates them from the host tissue
invasion features in malignant tumours
- growth accompanied by invasion and destruction of the surrounding tissue
- poorly demarcated from the surrounding normal tissue and a well defined ‘cleavage plane’ is lacking
- most malignant tumours are obviously invasive
metastasis
tumours that develop secondary to and discontinuous with the primary tumour
marks a tumour as malignant as benign neoplasms do not metastasise
exceptions of tumours that metastasise
exceptions are neoplasms of the glial cells in the CNS, called gliomas, and basal cell carcinomas of the skin. both are highly invasive forms of neoplasia but they rarely metastasise
angiogenesis
formation of new blood vessels
stages in formation of metastases
- malignant cell breaks down intercellular matrix
- malignant cell enters capillary
- malignant cells circulate round body in blood
- malignant cell adheres to blood vessel wall
- malignant cell travel into tissue at new site
- malignant cell divides to form metastasis at new site
3 cancer types
leukaemias
sarcomas
carcinomas
leukaemia
cancers of the blood or bone marrow
sarcomas
cancers of the connective or supportive tissue (bone, cartilage, fat, muscle, blood vessels) and soft tissues
sarcomas are rarer
carcinomas
cancers that arises from epithelial cells, these include breast, liver, lung, stomach etc.
cancer treatment strategies
surgery
radiotherapy
chemotherapy
differential sensitivity in treatment
want to kill cancer cells - not normal cells
benefit/harm = relief of cancer symptoms/treatment-related toxicity
therapeutic index
What’s different about cancer
metastasis
angiogenesis
antigens expressed
cancer cells grow and divide faster than normal cells
the main goal of antineoplastic agents
is to eliminate the cancer cells without affecting normal tissues (is the concept of differential sensitivity). In reality, all cytotoxic drugs affect normal tissues as well as malignancies - aim for a favourable therapeutic index (therapeutic ratio)
therapeutic index
the lethal dose of a drug for 50% of the population (LD50) divided by the minimum effective dose for 50% of the population (ED50)
therapeutic index = LD50/ED50
what do most conventional chemotherapy drugs and radiotherapy target and why
cell division
the main feature of cancer cells that they are growing fast or “proliferating”
factors that regulate the cell cycle and ensure a cell divides correctly
- before a cell divides, the DNA is checked to sure it has replicated correctly (if DNA does not copy itself correctly, a gene mutation occurs)
- this is done during the normal cell cycle
- the cell cycle regulates cell growth and division
- 4 stages: G1, S, G2, M
- M, mitosis is the point in the cycle where the cell divides into two
- cells can also go into G0, which is known as quiescence, cells no longer divide, quiescence is reversible
cell cycle - GAP 1
cell increases in size, produces RNA and synthesises proteins
cell cycle - GAP 0
cell will leave the cycle and stop dividing
cell cycle - GAP 2
cell will continue to grow and produce new proteins required for cell division
cell cycle - synthesis phase
DNA replication takes place
what controls the cell cycle
- cyclins are the proteins which control the progression through the cell cycle
- each gets turned on when required to allow progression through next phase
cyclin-dependent kinases
- CDKs signal to the cell that is ready to pass into the next stage of the cell cycle
- cyclins bind to CDKs, activating the CDKs to phosphorylate other molecules
regulation of CDKs
- CDKs controlled by inhibitors of the cell cycle
- many of these are tumour suppressor genes such as P21
- which are in turn controlled by oncogenes and tumour suppressor genes such as P53, which is a protein that regulates the cell cycle and hence functions as a tumour suppressor
cell cycle checkpoints that can lead to cell cycle arrest (to ensure damaged cells don’t go on to divide)
- checks on DNA damage and chromosome alignment
- cell either repair or die (apoptosis)
- in cancer cells often repaired but repair is faulty then cells progress and divide > genomic instability and mutation
- arrest is controlled by tumour suppressors p53 and pRB
treating cancers
- includes drugs that can stop cancer cells from dividing and induce apoptosis
- different drugs act at different phases of the cell cycle
