COD Cancer Flashcards

Question

How do cancer cells evade the immune system?

Answer 1

Loss of tumour antigens Downregulation of antigen-presenting molecules (APCs) Over-expression of immune checkpoint proteins and anti-apoptotic proteins

Answer 2

from inner mass of early embryo that can differentiate into different cell types during development

Answer 3

in regenerative tissue, replaces cells that mature and die

Answer 4

Cancer stem cells

Answer 5

Are are subpopulations within a tumour that are thought to initiate and maintain the cancer May be responsible for: Heterogeneity of tumours Tumour plasticity Migratory abilities Can be identified (and isolated) through various and/or tissue specific stem cell markers e.g. CD44 (breast and pancreas), CD133 (colon, prostate, brain) More likely to survive anti-cancer treatments May arise from deregulation of self-renewal pathways e.g. Wnt and Hedgehog

Answer 6

Driver mutation: confers growth/survival advantage Passenger mutation: does not confer any advantage!

Answer 7

``` Radiation Chemicals Infectious pathogen Endogenous reactions Mutations arise due to both DNA damage caused by carcinogens and additionally, errors/malfunctions in DNA repair mechanisms ```

Answer 8

Direct DNA damage Ionisation of atoms comprising DNA ``` Indirect DNA damage Radiolysis of H2O and ROS generation Hydroxyl radical H2O2 Superoxide radical ```

Answer 9

UVA - (wavelength 320-380 nm) UVB - (wavelength 290-320 nm) * most effective carcinogen UVC - (wavelength 200- 290 nm)

Answer 10

Most effective carcinogen Mutations induced cause bends in the DNA which are misread by DNA polymerase Causes 80% of skin cancers - squamous and basal cell carcinomas (some melanoma) p53 tumour suppressor commonly affected Risk factors – over exposure to the sun i.e. sunburn, sunbeds

Answer 11

An electrophilic (or electron deficient) form reacts with the nucleophilic sites (sites that can donate electrons) in the purine and pyrimidine rings of nucleic acids. Direct acting carcinogens (uncommon) Indirect acting carcinogens (common)

Answer 12

Reactive electrophiles Interact with nitrogen and oxygen atoms in DNA Examples include dimethyl sulphate and nitrogen mustards

Answer 13

Unreactive and water soluble Electrophilic centre produced by enzyme modification e.g. via processing by cytochrome p450 enzymes Interact with bases in DNA forming adducts Examples include polycyclic aromatic hydrocarbons (PAHs) (cigarette smoke) & aromatic or heterocyclic amines (cooked meats) Risk: smoking, diet high in cooked or processed meat, preservatives in processed food

Answer 14

A virus that can cause cancer DNA tumour viruses RNA tumour viruses (retroviruses)

Answer 15

Encode viral proteins that block tumour suppressor action Example: Human papillomavirus (HPV) degrades RB tumour suppressor leading to constitutive activation of the cell cycle oncogenic virus

Answer 16

Encode mutated forms of normal genes Example: Human T-cell lymphotropic virus (HTLV-1) (only virus known to be linked with human leukaemia) oncogenic virus

Answer 17

Cause chronic inflammation that helps promote cancer e.g. Helicobacter pylori infection can initiate gastric cancer Bacterial proteins affect cell signalling proteins that regulate cell proliferation, survival and invasion

Answer 18

They promote cell proliferation or cell survival Examples: components of signalling pathways driving cell proliferation ; anti-apoptotic proteins Effect of mutation – GAIN of function Dominant mutation Converts proto-oncogenes into oncogenes

Answer 19

Inhibit cell survival and/or negatively regulate cell proliferation Examples: apoptosis promoting proteins; CDK inhibitors; cell cycle checkpoint regulators Effect of mutation – LOSS of function Recessive mutation

Answer 20

Loss of entire chromosome Region containing normal gene is deleted Mutation in coding sequence which results in non-functional protein Chromosomal rearrangements – gene is disrupted Gene activity silenced by epigenetic changes Mutations in genes coding for chromatin-remodelling complexes e.g. SWI/SNF

Answer 21

``` Predisposition to develop cancer Hereditary retinoblastoma (loss of RB TS gene results in childhood retinal tumours and other tumours later in life) Familial adenomatous polyposis (FAP) (loss of APC gene – formation of colon polyps which if untreated could develop into malignant colon cancer ```

Answer 22

Repair or prevent DNA damage Examples: DNA repair enzymes Effect of mutation – LOSS of function Recessive mutation ``` Arise by deletion, point mutation or methylation Repair mechanisms affected DNA mismatch repair Nucleotide excision repair Double stranded DNA breaks ``` Can get inherited defects

Answer 23

The concentration of different cyclins varies in different stages of the cell cycle Cyclin is the regulatory subunit of the CDK Pairing of cyclins and CDKs is specific Examples: Cyclin D /CDK 4/6 CDKs are serine threonine kinases

Answer 24

G1 cyclins G1/S cyclins S phase cyclins M phase cyclins

Answer 25

Cyclin binding Phosphorylation & dephosphorylation Binding to CDK inhibitors e.g. p15, p16, p21 and p27

Answer 26

``` Guardian of the genome Transcription factor Multi-functional TS that can promote: Arrest in G1 and G2 phase Via production of p21 and p27 cdk inhibitors Apoptosis DNA repair with respect to DNA damage ```

Answer 27

1. Increased ligand production EGFR ligands particularly EGF are frequently over-expressed in cancer Occurs via autocrine stimulation 2. Increased EGFR receptor levels Can occur due to: Gene amplification Defective gene promoter activity (binding of p53 proteins) Defective receptor downregulation (inability to bind c-Cbl)

Answer 28

*****Mutations giving rise to constitutively active variant receptors A variety of mutations are known to exist and can be found in all areas of the receptor i.e. both extracellular and intracellular Example: EGFR variant III Loss of most of the extracellular binding domain Constitutively active (in absence of ligand) Prominent in the very aggressive brain tumour glioblastoma Strongly and persistently activates the PI3 kinase/Akt signalling pathway Increased cell survival, proliferation and motility Resistance to treatment

Answer 29

Intrinsic / mitochondrial route or extrinsic (death receptor mediated) route Intrinsic route most commonly disrupted in cancer

Answer 30

cytochrome c from the mitochondria | Regulated by a balance between molecules that promote apoptosis and those which inhibit apoptosis

Answer 31

pro - BAK, BAK, BAD | anti - BCL-2, BCL-XL = L is small