Cancer basics Flashcards
Neurological side-effect of chemotherapy?
Reduced cognition
Driver mutations?
TP53
Telomerase
RAS
What is offered to those with a TP53 mutation?
Annual whole body MRI
What are the normal functions of TP53?
Activates DNA repair
Arrests division if there’s DNA damage
Initiates apoptosis
What proportion of cancers have a TP53 mutation?
Over half
What are RAS oncogenes?
Proto-oncogenes stuck in proliferative ‘on-mode’ meaning the tumour does not need growth factor stimulation to divide
What does over-expression of telomerase permit?
Cellular immortality
Non-specific signs of cancer?
Cachexia Anaemia Tachycardia Tachypnoea Palpable metastases
What does a liquid biopsy of cell free circulating DNA grant?
Aggregate of all tumour cells in the population
What is TP53
A tumour suppressor gene
Gradings of ‘T’ in TNM?
0, 1, 2, 3, 4
Gradings of ‘N’ in TNM?
0, 1, 2, 3
Gradings of ‘M’ in TNM?
0, 1
Example of a type of cancer RAS mutation is associated with?
Pancreatic cancer
What is a proto-oncogene?
A gene that when mutated or over expressed contributes to the development of cancer, i.e. has the potential to give rise to an oncogene
What is a tumour suppressor gene?
A gene who’s loss contributes to the development of a cancer
Resistance to apoptosis achieved by what?
Loss of p53
Upregulation of pro-survival factors like Bcl-2
What occurs in 85% of human carcinomas?
Telomerase expression/activity is gained
Which protein do cancer cells lose allowing them to become more motile?
E-cadherin
List some common oncogenes:
Her2-neu RAS Myc Src Htert
List some common tumour suppressor genes:
P53
Rb
APC
Breast oncogene
Her2
Colorectal oncogene
Kras
Melanoma oncogene
BRAF
What type of mutation is an oncogene?
Gain of function
What type of mutation is in a defective tumour suppressor gene?
Loss of function
Mutation of which gene changes a normal colon epithelium to a small adenoma?
APC
Mutation of which gene changes a small adenoma to a large adenoma?
RAS
Mutation of which gene changes a large adenoma to a carcinoma?
PI3K
Cell cycle/apoptosis
TGF-beta
Hereditary breast cancer:
5-10%
BRCA1/2 (HPOC)
P53 (LFS)
Hereditary ovarian cancer:
15-20%
BRCA1/2 (HPOC) MMR genes (Lynch syndrome)
Hereditary colorectal cancer:
5-10%
MMR genes (Lynch syndrome) APC (FAP)
Hereditary melanoma:
5-10%
p16 (FAMM)
Hereditary medullary thyroid:
25%
RET (MEN2)
Hereditary retinoblastoma:
40%
RB1 (familial retinoblastoma)
Hereditary phaeochromocytoma:
30%
SDHx (familial paraganglioma and phaechromocytoma syndrome)
How does the chemotherapy carboplatin treat BRCA deficient tumours?
Introduces DNA cross links that the BRCA deficient cells cannot repair through homologous recombination (considered platinum therapy)
How do PARP inhibitors kill BRCA deficient cancer cells?
Introduce single strand breaks which form into double strand breaks that are toxic to the BRCA deficient cancer cell
Example of a PARP inhibitor?
Olaparib
How is PARP inhibition therapy used?
Maintenance therapy after chemotherapy
What causes Lynch syndrome?
Germline mutation in the DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2
What do tumour cells have in Lynch syndrome that makes them an immune target?
Mutator phenotype and micro-satellite instability (MSI-H, high antigenicity)
How do MSI-H tumours avoid immune recognition?
Expression of immunosuppressant molecules e.g. PD1
How do you restore the immune response to MSI-H tumours?
Use a PD1 inhibitor e.g. pembrolizumab
Epidermal growth factor receptor is over expressed in which cancer?
Non-small cell lung cancer, especially squamous cell carcinoma
What are Gefitinib and Erlotinib?
Tyrosine kinase inhibitors
What are Gefitinib and Erlotinib used to treat?
Non-small cell lung cancers (squamous) to block the EGFR pathway
What is EGFR in lung cancer?
Oncogene with driver mutations
Aflatoxin (produced by aspergillus)
Liver - hepatocellular carcinoma
Aniline dyes
Bladder - transitional cell carcinoma
Asbestos
Mesothelioma
Bronchial carcinoma
Nitrosamines
Oesophageal carcinoma
Vinyl chloride
Hepatic angiosarcoma
BRCA2 risks:
Breast cancer 70% (8% in men) Contralateral breast cancer 65% Ovarian cancer 20% Prostate cancer (25%) Pancreatic cancer (3%)
Action of cisplatin?
Targets DNA
Action of taxanes e.g. paclitaxel?
Targets microtubules
Non-cytotoxic therapies:
Targeting tyrosine kinase
Monoclonal Abs to cell surface receptors
Immune checkpoint inhibitors
Action of nivolumab?
Anti-PDL-1 used to treat melanoma
Side effects of EGFR-targeting drugs?
Rash and diarrhoea
Side effects of trastuzumab (herceptin)?
Cardiac toxicity
Side effects of checkpoint inhibitors?
AI colitis
Pneumonitis
What is Li-Fraumeni syndrome?
Autosomal dominant
Germline mutations to the p53 tumour suppressor gene
Diagnosed when: 1st degree relative develops cancer <45 and another relative does <45/sarcoma at any time
