L1.1 cancer epigenetic Flashcards
what are the four stages of cancer progression
initiation, promotion, progression and metastasis
what is initiation of cancer
the change of mutations arising spontaneously or induced by exposure to an agent.
what happens the promotion stage of cancer progression
cells actively proliferating accumulate
what happens during the progression stage of cancer
genetic and phenotypic changes occur are fast increase in tumour size
what is metastasis
spread of cancer cells to other parts of the body through blood or lymph
what is the definition of cancer
Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the body
what are the 10 hallmarks of cancer
evading growth suppressors
activating invasion and metastasis
sustained proliferative signalling
avoiding immune destruction
tumour promoting inflammation
genome instability and mutation
inducing angiogenesis
enabling replicative immortality
deregulating cellular energetics
resisting cell death
what are some of the DNA methylation changes detected in cancer cells?
- gene specific hypo- and hyper-methylation
- Global hypomethylation across the genome
- Increase incidence of mutations
repeat sequences containing transposable elements are hypo or hyper methylated?
hypomethylated
what are transposable elements?
unstable DNA which are heavily methylated and mobile can cause genome instability
what type of cells are stem cells
pluripotent
what is a pluripotent cell
undifferentiated and can differentiate into different cell linages
what are the characteristics of cancer cells within a tumour
undifferentiated and have capacity to self-renewal.
resistant to chemo
which two ways can cancer stem cells originate by?
- De-differentiation of somatic or differentiated cancer cells
- Mutations and epigenetic changes in normal stem cells or progenitor cells can lead to their formation.
what are totipotent stem cells
give rise to hundreds of cells found in the embryo and placenta
what are multipoint stem cells
can develop into a limited number of cell types within a linage
epigenetic abmormailities provide cancer cells with their key phenotypic characterstics such as
- Enhanced plasticity
- Loss of cell identify
- Differentiation and ability to self-renew
epigenetic abnormalities are associated with…
the development and progression of cancer
how can epigenetics be used in detection and diagnosis
detection of hypomethylated genes in biological fluid is a biomarker for early diagnosis
how can epigenetics be used in prognosis
whole genome wide methylation can be indicators of prognosis
how can epigenetics be used in prediction
hypermethylation of some genes has been identified as an independent predictive factor
how can epigenetics be used in follow up for leukaemia
in Leukaemia cells p15 methylation initiates proliferation so if in follow up this gene is methylated it indicates cancer recurrence.
what are the negative effects of chemotherapy
resistant to treatment, negative quality of life, toxicity, development of secondary malignancies.
epigenetic drugs are referred to as …
small molecule inhibitors or epidrugs
why do drugs target epigenetic machinery
- It is well-established that epigenetic dysregulation has a key role in origin and progression of all cancers
- Unlike mutations epigenetic modifications are reversable
small molecule inhibitors are designed to do what?
target enzymatic epigenetic regulators which place or remove an epigenetic tag
what is the aim of epigenetic drugs
to activate tumour suppress genes, deactivate oncogenes, prevent proliferation and trigger apoptosis in cancer cells by targeting and altering the epigenome of the cancer cell.
what do DNMT inhibitors do
prevent hypermethylation of genes, stimulates reprogramming, results in cell death
what are the two types of DNMT inhibitors
Nucleoside analogs
Non-nucleoside DNMTi
what are Nucleoside analogs
replication dependent because it is incorporated into DNA/RNA synthesis
what are Non-nucleoside DNMTi
small molecules that are not incorporated into DNA to inhibit function of enzymes. these block catalytic sites of the enzyme
what are HDAC inhibitors. And examples
small molecule target and inhibit the activity of histonedeacetyltransferase which makes DNA less accessible for transcription which suppresses the genes. Results In apoptosis
Vorinostat and romidepsin
Describe what DNMT is and what is the role of DMNTi and examples
DMNTi is an inhibitor which inhibits the enzymes that methylate DNA to prevent tumour suppressor genes from being methylated and suppressed.
Decitabine and vidaza
