Hallmarks of Cancer Flashcards
what does the T mean in the TNM naming system?
describes the size of the tumour, and how far is has spread into nearby tissue
what does the N mean in the TNM naming system?
describes if there is any cancer cells in the lymph nodes
what does the M mean in the TNM naming system?
describes if the cancer has spread to another part of the body
what are the biomedical cancer risk factors?
genetic susceptibility and hormonal factors in females
what are the lifestyle risk factors for cancer?
smoking, alcohol, obesity, physical inactivity, chronic infections and poor diet
what are the environmental risk factors of cancer?
sunlight, radiation, occupational exposure, pollution
what is stage 0 cancer?
very small and benign
what is stage 1?
small and contained within the organ of origin
what is stage 2?
tumour larger than stage 1, but not spread into surrounding tissues, may have spread into closely lymph nodes depending on cancer
what is stage 3?
cancer is larger, may have spread into surrounding tissues and there are cancer cells in lymph nodes nearby
what is stage 4?
means the cancer has spread from where it originated, such as the liver or lung, is also called secondary/metastatic cancer
in what 2 ways is cancer classified?
by the type of tissue in which it originated and the location where it developed
what is carcinoma?
malignant neoplasm of epithelial origin in internal or external lining of the body
what is adenocarcinoma?
a carcinoma that developed in an organ or gland
what is squamous cell carcinoma?
develops in a squamous cell
what is sarcoma?
cancer that originates in supportive and connective tissue such as bones, tendons, cartilage muscle and fat
what are the features of sarcoma?
generally occur in young adults and resemble the tissue in which they grow
what is myeloma?
originates in the plasma cells of the bone marrow
what is leukaemia?
cancers of the bone marrow
why is a person with leukaemia prone to infection?
overproduction of white blood cells that do not perform as they should so cannot fight infection
what is lymphoma?
cancer that develops in glands or nodes of lymphatic system, blood vessels and organs that purify bodily fluids
what is lymphoma classified as?
hodgkin or non-hodgkin
what are the hallmarks of cancer?
sustaining proliferative signalling, evading growth suppressors, activating invasion and metastasis, enabling replicative immortality, inducing angiogenesis and resisting cell death
what is growth signal autonomy?
normal cells need external signals in order to divide, cancer cells circumvent this leading to uncontrolled growth, and can also create their own growth factors
how can cancer cells cause hyper responsiveness to growth signals?
they have the ability to synthesise and secrete their own growth factors and can have mutations in the GF receptors that increase the amount present on cell surface
how can cancer cell GF receptors be permanently switched on?
the receptor can become structurally altered causing a lack of regulatory regions
what is Ras?
a key signalling pathway protein
what is an oncogene?
genes that promote automomous growth in cancer cells
how do oncogenes cause unregulated growth?
they produce oncoprotein which do not have important regulatory elements and their production in the transformed cells does not depend on growth factors or other external signals
why is retinoblastoma classified as a tumour suppressor protein?
because at the molecular level, all antigrowth signals are fuelled through the retinoblastoma protein
how does retinoblastoma prevent cell growth?
binds to E2F so that it is not free to then bind to transcribe DNA
how is the intrinsic pathway of apoptosis activated?
by stress or damage to the cell
what proteins are activated by intrinsic apoptosis?
BH3-only proteins
how are BAX and BAK activated?
by pro-apoptotic BH3-only proteins
what do BAX and BAK do?
cause mitochondrial outer membrane permeability which is a point of no return for apoptosis allowing cytochrome C init the cytoplasm
what is the role of cytochrome C in apoptosis?
acts as a signalling molecule in cytoplasm which prompts formation of apoptosome
what follows formation of apoptosome in apoptosis?
apoptosome turns pro-capsase-9 into capsase-9 which actives capsase -3 and -7
what role do -3 and -7 have in apoptosis?
they begin the breakdown of cellular materials and -3 condenses and breaks down cellular DNA
what is p53 responsible for?
detecting DNA damage, chromosome abnormalities and arresting cell cycle to initiate repair
how does p53 induce apoptosis?
increases production of apoptotic protein BAX
how can cancer cells compromise the activity of p53?
increasing inhibitors of p53 or silencing the activators of p53 which reduces apoptosis
how does increased telomerase in cancer cells increase replication capability?
telomerase maintains the length of the telomere and so cancer cells are able to divide more times as they do not have a Hayflick limit
what is angiogenesis?
process through which new blood vessels form from pre-existing blood vessels
how can tumours gain their own blood supply?
release chemical signals that stimulate angiogenesis
what are the immune evasion strategies of cancer cells?
release of immunosuppressive factors, T cell checkpoint dysregulation, recruitment of immunosuppressive cells, ineffective presentation of tumour antigens, tumour microenvironment
what is the Warburg effect?
altered cellular energetics, where cancer cells have an increased glucose uptake and lactate production which allows them to survive in hypoxic conditions
how are tumours and inflammation linked?
by NFkB and TAMs
what is NFkB?
transcription factor that is key in inflammation responses
how does NFkB become free to enter a nucleus?
IkB kinase phosphorylates IkBa which means it can no longer hold NFkB in an inactive state and therefore it is free to enter
what does NFkB do once it enters the nucleus?
activates genres that promote cell growth, survival, migration and the formation of new blood vessels
how is a positive feedback loop of NFkB form?
activation of NFkB in immune cells causes production of molecules that activate NFkB in cancer cells, which in turn induce molecules that attract more immune cells
what does a NFkB feedback loop cause?
uncontrolled growth with immune cells actively enhancing hallmark capabilities of cancer cells
what do TAMs do to encourage tumour growth?
supplies growth factors
what do TAMs produce?
EGF, FGF and small molecules such as cytokine, primary IL-6 and TNF
what growth factors are used by a tumour to carry out angiogenesis?
vascular endothelial growth factor and platelet derived growth factor
how can oxygen derived conditions be beneficial to TAMs?
because they can activate angiogenesis through the hypoxia response pathway
how can VEGF create a feedback loop?
attracts TAMs to a tumour which causes more VEGF to be produced
how can TAMs and matrix degrading enzymes help metastasis?
they help to degrade the ECM of a cell which aids in the invasion and spread of cancer cells
what is an example of a matrix degrading enzyme?
metalloproteases
how do TAMs suppress the immune system?
produce immunosuppressive molecules, allowing the tumour to evade the immune system, and release cytokines that attract other immune cells
