cancer and cancer biology Flashcards
what is cancer
a disease in which an abnormal group of cells grow uncontrollably, disregarding the normal rules of cell division
what are the hallmarks of cancer
sustaining proliferative signalling, immortality, evading growth suppressors, invasion and metastasis, angiogenesis, resisting cell death
how do cancers sustain proliferative signalling
eR2B receptors form homodimers and phosphorylated to activate Ras pathway - mutation of Ras = active!
how do cancers evade growth suppressors
- G1 checkpoint mutations in cyclins/CKDs/CDKIs
- Rb protein mutation - usually acts as a break to inhibit entry to S phase - phosphorylation allows cell to continue, deletion/mutation causes cell division because of E2F mediated transcription
- P53 mutations - no apoptosis or DNA fixing
how do cancer cells resist cell death
P53 mutation, accumulation of damaged DNA but no apoptosis
how do cancer cells become immortal
telomerase - enzyme which adds TTAGGG to breaking telomeres - upregulated in cancer cells so division never stops
how do cancer cells induce angiogenesis
tumour cells release proangiogenic factors (VEGF)
endothelial cells secrete mmp to digest tumour extracellular matrix
endothelial cells form a new aberrant blood vessel in the tumour
- disorganised, leads to hypoxic and normoxic environments
how do cancer cells cause invasion and metastasis
- proteolytic degradation helps cancer cells break off (E-cadherin)
- macrophages secrete chemokines and tumours secrete factors to affect macrophage function
- pericytes secrete CXCL12 to cause migration
- cells can die, become dormant or migrate to new tissues
what are the emerging hallmarks of cancer
deregulating cellular energetics, genome instability and mutation, avoiding immune destruction, tumour promoting inflammation
how do cancer cells deregulate cellular energetics
convert glucose to lactate irrespective of the presence of oxygen
how do cancers avoid immune destruction
- stop MHC processing to prevent the loading of antigenic peptides to MHC
- upregulated PDL-1 to inhibit T cells
- release cytokines to cause immunosuppression
how do tumour cells promote inflammation
- they release chemotactic factors to attract monocytes which differentiate into macrophages (TAM - tumour associated macrophages)
- TAMs release angiogenic factors, metalloproteases and mitogenic factors
incidence of cancer
approx. 1000 new cases daily, 450 deaths daily, 50% survival
incidence and risk factors of lung cancer
- 3rd most common in UK
- age/gender, smoking, gas exposure and cancer history
screening and treatment of lung cancer
- screening smokers aged 55-74
- treat with chemo, radio, surgery or chemo radio
incidence and risk of breast cancer
- 150 + people diagnosed a day
- weight, alcohol, contraceptives, dense tissue, age, genes, hormones and ethnicity
screening and treatment of breast cancer
mammograms for women 50-70 years
- surgery, chemo, radio, HRT, cancer drugs, bone strengthening
incidence and risk factors of colon cancer
- 42 000 cases daily
- age, family history, genetics, diet, lifestyle
screening and treatment for colon cancer
faecal immunochemical test - for small traces of blood
- surgery or chemotherapy
incidence and risk factors for prostate cancer
52 000 a year
- age, ethnicity, obesity and height
screening and treatment for prostate cancer
rectal examinations
- risk dependent!
- low risk is watch and wait, surgery and then radiotherapy
acute myeloid leukaemia
starts from monocytes in the bone marrow, commonly in over 75 y/os, mainly treated with cancer drugs, transplants and radiotherapy
chronic myeloid leukaemia
develops from myeloid stem cells, mainly treated with targeted cancer drugs - caused by BCR-abl gene
acute lymphoblastic leukaemia
starts from lymphocytes in bone marrow, more common in men and treated by chemotherapy and stem cell transplant
chronic lymphocytic leukaemia
develops from lymphoid blood stem cells, mainly treated with bruton tyrosine kinase inhibitors
carcinoma
most common cancer type, arises from cells covering body surfaces
sarcomas
originate from supporting tissues - highly malignant
lymphomas
arise in the lymph and immune system tissues
leukaemia’s
cancer of white blood cells that proliferate in the white bone marrow
how does viral DNA cause cancer
viral genome persists in infected cells as an episome, HHV promotes expression of proteins that promote proliferation (direct)
how does viral RNA cause cancer
retrotranscribed into DNA to provide a gene that alters growth
how does a virus cause cancer indirectly
virus acts outside the cell and triggers chronic inflammation
carcinogenesis
- initiation
- promotion
- progression
- metastasis
