W8 Hallmarks of cancer (GN) Flashcards
What is a Tumour/Neoplasm?
how does a tumour originate?
benign means?
malignant means?
➢Abnormal new growth of tissue that possess no physiological/purposeful
function and derived from by uncontrolled and disorganised cell proliferation
- Tumour is initiated in a single cell by the progressive accumulation of mutations
in genes that are crucial in cell proliferations, survival and invasion. - Not all tumours are cancerous
Benign tumour growth
▪ Slow, limited and localised
Malignant/Cancer growth
▪ Invasive and malignant
Benign tumour vs malignant cancer?
Benign
* Non-cancerous cells
▪ Slow growth rate
▪ Encapsulated → stay localized
▪ No invasive
▪ Retention of cell specialisations
▪ Cells with normal shape
▪ Rarely fatal (good prognosis)
Malignant (CANCER)
* Cancerous → invasive
▪ Rapid growth rate
▪ Invade tissues
▪ Metastasise to other far organs
▪ Poorly differentiated/specialised
▪ Larger cells with darker shape
▪ Life-threating, (bad prognosis)
The 4 main classes and relative suffixes of tumours are?
-
Carcinomas
-cells that cover external and internal organs or glands -
Sarcomas
-cells in the supporting tissues: bone, cartilage, fat, connective tissue, muscle -
Lymphomas
-start in the lymph nodes & tissues of the immune system -
Leukemias
-start in the immature blood cells that grow in the bone marrow
What are some types of tumours do not fit into the major classifications
- Gliomas, Neuroblastoma, Schwannomas
and Medulloblastomas, Melanoma
-specific cells of the Central and Peripheral
nervous system
What are the different kinds of cancer prefixes?
adeno- gland
chondro-cartilage
erythro- red blood cell
hemangio- blood vessels
hepato- liver
lipo- fat
lymph- lymphocyte
melon- pigment cell
myeloma- bone marrow
mayo- muscle
osteo- bone
What are the Different Kinds of Cancer?
Incidence of cancer in UK – both sexes and all ages in 2017:
➢ breast (15%),
➢ prostate (13.5%),
➢ lung (13.1%)
➢ bowel (11.5%) cancers
* together account for 53% of all new cancer cases
Mortality from cancer in UK – both sexes and all ages in 2017
➢ lung (21%),
➢ bowel (11%),
➢ prostate (7%)
➢ breast (7%) cancers
What are the traditional hallmarks of cancer? (6)
- Sustaining proliferative signalling
- Evading growth suppressors
- Activating invasion and metastasis
- Enabling replicative immortality
- Introducing angiogenesis
- Resisting cell death
What are the Complementary hallmarks of cancer? (4)
- Deregulating cellular energetics
- Genome instability and mutation
- Avoiding immune destruction
- Tumor-promoting inflammation
What is the ‘normal’ cell cycle?
- 3 cell cycle checkpoints
- Checkpoint progression depends on
cyclically activated Cyclin-dependent
protein kinases (Cdks) bound to cyclin - Proliferative signals stimulates the
synthesis of cyclins that activate CDKs - Cyclin/CDKs phosphorylates key proteins
Normal cell proliferative signalling:
- Growth factors, Intracell., Factors =
- Cyclin/CDKs activation, Activation of protooncogenes
= Pathways for checkpoint progression - Anti growth factors, DNA damage
- = Activation of tumor suppressor genes
- = Pathways to block cell cycle, Enter G0 phase or apoptosis
Cancer Hallmark 1 – sustaining proliferative signalling
How are the first 2 cell signalling steps reprogrammed?
Cancer cells acquire growth factor-proliferation autonomy in a variety of ways, reprogramming the first two cell signalling steps
- Key mutations in oncogenes to stimulate and sustain cell division
Reception → Cancer cells become hyperresponsive
▪ release of extracellular growth factors
(autocrine/paracrine activation → positive feedback)
▪ Overexpression of extracellular receptors of those signals
Transduction → alteration of signalling components (i.e. RAS oncogene)
▪ Constitutive activation of downstream signalling pathways
▪ Defective activation of negative feedback regulatory mechanisms (off-switches)
Cancer Hallmark 2 – evading growth suppressor:
What do ca cells become irresponsive to?
What signalling components are altered?
What are inactivated?
- DNA changes to evade cell progression inhibition
➢ Reception
Cancer cells become irresponsive to antiproliferative signals
▪ Inactivation or down expression of receptors sensing these signals
* DNA changes to evade cell progression inhibition
➢Transduction → alteration of signalling components (e.g. p53 and other tumour suppressor proteins inactivation)
▪ Tumour suppression inactivation activated by growth suppressor signals → Blocking transition to G0 phase or cell cycle transition
Apoptosis in normal tissue?
What is apoptosis? (simple)
What is the intrinsic pathway?
extrinsic pathway
- Apoptosis → physiological and neat process inducing a programmed cell death induced by external and internal stimuli
Intrinsic pathway:
▪ Internal signals releasing cytochrome C from mitochondria into the cytosol
Extrinsic pathway::
▪ External signals (e.g. TNF-α) recognised by death receptors
Anti-apoptotic (survival) stimuli = low and Pro-apoptotic stimuli = high
Cancer Hallmark 3 – resisting cell death
What are the Driver mutations to evade apoptosis?
inc in?
dec in?
what are inactivated?
➢INC anti-apoptotic regulators (e.g. Bcl-2)
➢ DEC pro-apoptotic regulators
➢Inactivating apoptotic signalling proteins
(caspases – cleaving multiple substrates)
Telomeres and senescence
What are telomeres?
What happens to telomeres after each DNA replication?
What happens when telomeres become too short? (2)
- Regions of repetitive DNA sequences at chromosome ends
- Each DNA replication shortens telomeres (25-200 bps)
- When telomeres become too short, chromosomes can no longer be replicated → Senescence (cell arrest) → and Crisis (apoptosis)
