intro to cancer Flashcards
what is cancer?
the unwanted proliferation of certain cells (unwanted cell growth)
- Not just one disease but a collection of diseases with the shared underlying features of uncontrolled cell growth and invasion
what are the types of cancers and where does it effect?
carcinoma - epithelial - breast,lung, liver cancer
sarcoma - connective tissues - bone, muscle, blood vessel
myeloma - bone marrow - plasma cells
leukaemia - bone marrow - WBC, erythrocytes
Lymphoma - lymph nodes/glands - spleen, tonsils, thymus
-oma - benign tumours
what is neoplasm?
: new disorganised growth with net increase in numbers of dividing cells (i.e. a tendency to excessive, uncontrolled growth). Synonymous with the more familiar term ‘tumour’ (swelling).
-precancerous tissues
what is tumor
: a mass of abnormal cells.
what is benign tumors?
these enlarge but do not invade the surrounding tissue, nor spread beyond their initial site.
what is malignant tumors?
those that are not benign and spread beyond their initial site. These are the more dangerous tumours.
what is metastasis?
invasion of a tumour to its surrounding tissue and spread beyond the original site.
what is carcinogenesis?
the process of forming a cancer (via carcinogens).
how is cancer cell formed?
Cancer cell is formed when a normal cell undergoes specific changes that allow it to proliferate without normal limit and spread to surrounding and/or distant tissues
Multiple changes are usually required to transform a “normal cell” into a “cancer cell”
Inherited susceptibility and/or lifestyle influences cancer progression
what is normal cell proliferation and why?
Ongoing throughout life to allow development, repair or regeneration of tissues
Cell division is regulated at a number of different levels to ensure that it is a tightly regulated process
what is the phases of cell cycle?
-M phase: mitosis and cytokinesis phase - prophase, metaphase, anaphase and telophase.
GAP 0 - quiescent (resting) cells
GAP 1 - RNA and protein synthesis req’d for S phase
S phase - DNA synthesis
GAP 2 - RNA and protein synthesis req’d for M phase
how is the cell cycle regulated?
The activity of cyclin:CDK complexes is regulated at multiple levels:
- Expression of regulatory cyclin component of complex
i.e. Expression and activity of the factors that control cyclin expression (i.e. E2F transcription factors and pRB proteins)
Regulation of the activivty of the cyclin:CDK complex (i.e. phosphorylation/de-phosphorylation events by CDC25 phosphatases)
Direct inhibition of complex activity cyclin-dependent kinase inhibitors (i.e. p27)
cell cycles can be regulated positively and negatively ( cell cycle inhibitors)
what are the cell cycle checkpoints
M - anaphase blocked if chromatid are not properly assessmbled on mitosis spindle
G1 - DNA damage checkpoint: entrance into S is blocked if genome is damaged.
S- DNA damage checkpoint : DNA replication is halted if genome is damaged
G2 - entrance into M blocked if DNA replication is not completed.
what are the hallmarks of cancer
self sufficiency in growth signals
insensitivity to anti growth signals
evading apoptosis
limitless replicative potential
sustained angiogenesis
tissue invasion and metastasis
what is oncogene?
Oncogene is the term given to genes which, when mutated or overexpressed, can cause cancer. Mutations in proto-oncogenes lead to a gain of function.
Many oncogenes are involved in the regulation of cell proliferation and lead to growth signals to be constantly turned on, even in the absence of any actual signal.
hallmark 1 - gains growth factor
what is ras
Ras was one of the first oncogenes discovered. In the presence of growth signals, normal Ras (the proto-oncogene) is activated and triggers other signalling events that lead to cell proliferation.
In cancer, Ras is often mutated (and becomes an oncogene) and is switched on all the time.
This leads to constant signalling to promote cell proliferation, even in the absence of a growth factor or other signal.
RAS IS transmitting messages downstream and is a growth factor
Ras is the most common oncogene found
in cancer; 20-30% of all tumours have a mutant version of Ras that is permanently switched on.
Other oncogenes include Bcr-Abl, myc, Src and PI3 kinase. In all cases oncogenes have increased activity and lead to increased cell proliferation in the absence of specific growth signals (i.e. gain independence from growth factors).
shy is oncogenes important drug target?
Oncogenes are an important drug target as blocking their function should stop the proliferation of cancer cells.
what is imatinib?
Imatinib is a tyrosine
kinase inhibitor that
prevents growth factor
signals promoting cell
proliferation
Hallmark 1: gains growth factor independence
what is its role?
Cell loses requirement for growth factors to stimulate cell division (i.e. they gain an oncogene)
This might include:
Secretion of growth factor normally secreted by surrounding tissue
Mutation in growth factor receptor so it is constitutively activated
Mutation of components of signaling pathways or transcription factors activated by growth factors
what is Human epidermal growth factor receptor 2 (HER2) amplified in ?
breast cancer
gastric
ovarian
prostate
what is the significance of HER2 expression?
Her2 positive cancers are typically more aggressive
It is associated with early progression, recurrence and poor prognosis
Trastuzumab (Herceptin) blocks Her2 receptor
Hallmark 2: insensitivity to growth inhibitors
what is its role?
Cell loses ability to control abnormal cell proliferation
Might result from alterations in cell cycle regulation
- Loss of tumour suppressor genes (i.e. pRb)
- Upregulation of positive cell cycle regulators (i.e. CDC25 or cyclins )
what is the function of the tumor supressor gene?
Tumour suppressor genes perform the opposite function to oncogenes in that they stop tumours from forming.
In many cases, two-hits are required to inactivate a tumour suppressor gene.
