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Cancer basics Flashcards

1
Q

Neurological side-effect of chemotherapy?

A

Reduced cognition

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2
Q

Driver mutations?

A

TP53
Telomerase
RAS

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3
Q

What is offered to those with a TP53 mutation?

A

Annual whole body MRI

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4
Q

What are the normal functions of TP53?

A

Activates DNA repair
Arrests division if there’s DNA damage
Initiates apoptosis

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5
Q

What proportion of cancers have a TP53 mutation?

A

Over half

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6
Q

What are RAS oncogenes?

A

Proto-oncogenes stuck in proliferative ‘on-mode’ meaning the tumour does not need growth factor stimulation to divide

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7
Q

What does over-expression of telomerase permit?

A

Cellular immortality

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8
Q

Non-specific signs of cancer?

A 
Cachexia
Anaemia
Tachycardia
Tachypnoea
Palpable metastases
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9
Q

What does a liquid biopsy of cell free circulating DNA grant?

A

Aggregate of all tumour cells in the population

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10
Q

What is TP53

A

A tumour suppressor gene

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11
Q

Gradings of ‘T’ in TNM?

A

0, 1, 2, 3, 4

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12
Q

Gradings of ‘N’ in TNM?

A

0, 1, 2, 3

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13
Q

Gradings of ‘M’ in TNM?

A

0, 1

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14
Q

Example of a type of cancer RAS mutation is associated with?

A

Pancreatic cancer

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15
Q

What is a proto-oncogene?

A

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

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16
Q

What is a tumour suppressor gene?

A

A gene who’s loss contributes to the development of a cancer

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17
Q

Resistance to apoptosis achieved by what?

A

Loss of p53

Upregulation of pro-survival factors like Bcl-2

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18
Q

What occurs in 85% of human carcinomas?

A

Telomerase expression/activity is gained

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19
Q

Which protein do cancer cells lose allowing them to become more motile?

A

E-cadherin

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20
Q

List some common oncogenes:

A 
Her2-neu
RAS
Myc
Src
Htert
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21
Q

List some common tumour suppressor genes:

A

P53
Rb
APC

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22
Q

Breast oncogene

A

Her2

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23
Q

Colorectal oncogene

A

Kras

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24
Q

Melanoma oncogene

A

BRAF

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25
What type of mutation is an oncogene?
Gain of function
26
What type of mutation is in a defective tumour suppressor gene?
Loss of function
27
Mutation of which gene changes a normal colon epithelium to a small adenoma?
APC
28
Mutation of which gene changes a small adenoma to a large adenoma?
RAS
29
Mutation of which gene changes a large adenoma to a carcinoma?
PI3K Cell cycle/apoptosis TGF-beta
30
Hereditary breast cancer: | 5-10%
BRCA1/2 (HPOC) | P53 (LFS)
31
Hereditary ovarian cancer: | 15-20%
``` BRCA1/2 (HPOC) MMR genes (Lynch syndrome) ```
32
Hereditary colorectal cancer: | 5-10%
``` MMR genes (Lynch syndrome) APC (FAP) ```
33
Hereditary melanoma: | 5-10%
p16 (FAMM)
34
Hereditary medullary thyroid: | 25%
RET (MEN2)
35
Hereditary retinoblastoma: | 40%
RB1 (familial retinoblastoma)
36
Hereditary phaeochromocytoma: | 30%
SDHx (familial paraganglioma and phaechromocytoma syndrome)
37
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)
38
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
39
Example of a PARP inhibitor?
Olaparib
40
How is PARP inhibition therapy used?
Maintenance therapy after chemotherapy
41
What causes Lynch syndrome?
Germline mutation in the DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2
42
What do tumour cells have in Lynch syndrome that makes them an immune target?
Mutator phenotype and micro-satellite instability (MSI-H, high antigenicity)
43
How do MSI-H tumours avoid immune recognition?
Expression of immunosuppressant molecules e.g. PD1
44
How do you restore the immune response to MSI-H tumours?
Use a PD1 inhibitor e.g. pembrolizumab
45
Epidermal growth factor receptor is over expressed in which cancer?
Non-small cell lung cancer, especially squamous cell carcinoma
46
What are Gefitinib and Erlotinib?
Tyrosine kinase inhibitors
47
What are Gefitinib and Erlotinib used to treat?
Non-small cell lung cancers (squamous) to block the EGFR pathway
48
What is EGFR in lung cancer?
Oncogene with driver mutations
49
Aflatoxin (produced by aspergillus)
Liver - hepatocellular carcinoma
50
Aniline dyes
Bladder - transitional cell carcinoma
51
Asbestos
Mesothelioma | Bronchial carcinoma
52
Nitrosamines
Oesophageal carcinoma
53
Vinyl chloride
Hepatic angiosarcoma
54
BRCA2 risks:
``` Breast cancer 70% (8% in men) Contralateral breast cancer 65% Ovarian cancer 20% Prostate cancer (25%) Pancreatic cancer (3%) ```
55
Action of cisplatin?
Targets DNA
56
Action of taxanes e.g. paclitaxel?
Targets microtubules
57
Non-cytotoxic therapies:
Targeting tyrosine kinase Monoclonal Abs to cell surface receptors Immune checkpoint inhibitors
58
Action of nivolumab?
Anti-PDL-1 used to treat melanoma
59
Side effects of EGFR-targeting drugs?
Rash and diarrhoea
60
Side effects of trastuzumab (herceptin)?
Cardiac toxicity
61
Side effects of checkpoint inhibitors?
AI colitis | Pneumonitis
62
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

Cancer (10 decks)

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