Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

302 Scientific basis of medicine > Cancer 4) Principles of treatment > Flashcards

Cancer 4) Principles of treatment Flashcards

1
Q

What are the types of chemotherapy drugs?

A 
Alkylating agents
Antimetabolites
Mitotic inhibitors
Tumour antibiotics
DNA topoisomerase inhibitors
All-trans retina acid and HDAC inhibitors
Hormone and hormone antagonists
Agents inhibiting DNA repair: PARP inhibitors (olaparib)
Inhibitors of DNA methylation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the classes of alkylating agents?

A

Nitrogen mustard based
Tetrazines
Non-classic
Platinum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Give examples of nitrogen mustard based alkylating agents

A 
Chlorambucil
Mechlorethamine
Cyclophosphamide
Melphalan
Bendamustine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Give examples of tetrazine alkylating agents

A

Dacarbazine (DTIC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the mechanism of alkylating agents?

A

Cause DNA alkylation and cross linking

Intra and inter strand cross linking of DNA which stops fork replication and causes mitotic catastrophe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Give an example of a non-classic alkylating agent

A

Procarbazine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Give examples of platinum-based alkylating agents

A

Cisplatin
Carboplatin
Oxaliplatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Give an example of antimetabolites

A 
Methotrexate
Pemetrexed
6-mercaptopurine
5-fluorouracil
Capecitabine
Cytosine arabinoside
Gemcitabine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Give the 2 types of mitotic inhibitors and examples of each

A

Taxans: docetaxel (taxotere), paclitaxel (taxol)

Vinca alkaloids: vinblastine, vincristine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do vinca alkaloids work?

A

Disrupt microtubules leading to mitotic arrest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the 2 types of tumour antibiotics and give examples?

A

Anthracyclines: doxorubicin, daunorubicin

Non-anthracyclines: bleomycin, dactinomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do anthracyclines work?

A

Topoisomerase II dependent DNA cleavage
Inhibits DNA and RNA synthesis by intercalating between bases of DNA and RNA strands which inhibits activity of DNA and RNA polymerase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the 2 types of DNA topoisomerase inhibitors and give examples

A

I (camptothecin): irinotecan, topotecan

II (podophyllotoxins): etoposide, mitoxatrone, teniposide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Give examples of hormone and hormone antagonists chemo drugs

A

Prednisone
Tamoxifen
Aromatase inhibitors
Abiraterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Give examples of inhibitors of DNA methylation

A

Zebularin
Azacytidine
5-aza-2’-deoxycytidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the side effects of chemotherapy?

A 
Pain
Neuropathy
Hair loss
Weakened immune system
Trouble breathing
Bruising and bleeding
Rashes
Nausea and vomiting
Constipation, diarrhoea
Mouth sores
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the side effects of nitrogen mustard?

A

BMT
Nausea and vomiting
Leukemogenic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the side effects of vincristine?

A

Neurotoxicity
Constipation
ANS disturbance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the side effects of procarbazine?

A 
BMT
Nausea and vomiting
Leukemogenic
Infertility
Psychotic reactions
Hypertensive crisis with MAOi
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the side effects of cyclophosphamide?

A

BMT - thrombocytopenia
SIADH
Nausea and vomiting
Bladder toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the side effects of chlorambucil?

A

BMT - neutropenia and anaemia
Nausea and vomiting
Leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the side effects of vinblastine?

A

BMT - neutropenia
Mucositis
Hypertension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the side effects of doxorubicin?

A 
BMT
Alopecia
Nausea and vomiting
Diarrhoea
Cardiac
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the side effects of bleomycin?

A

Fever
Skin toxicity
Pulmonary toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the side effects of DTIC?

A

BMT
Flu-like syndrome
Hepatic vein thrombosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the side effects of etoposide?

A

BMT - leukopenia and neutropenia

Leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the side effects of cisplatin?

A

Neurotoxicity
Ototoxicity
Nephrotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Why do most of the chemotherapy agents cause bone marrow toxicity and GI disturbance?

A

These are sites associated with high levels of normal cell division

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Give examples of targeted antibodies

A

Rituximab
Ofatumumab
Obinutuzumab
Alemtuzumab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the mechanism of rituximab?

A

Binds to CD20 on surface of B cells
Attracts macrophage which engulf tumour B cell
Complement fixation which attracts NK cells that deploy cytotoxic granules to kill the B cell

31
Q

How does ofatumumab work?

A

Induces antibody dependent cytotoxicity

32
Q

How does obinutuzumab work?

A

Has cytotoxic effects of its own. Binds to CD20 receptor causing antibody to induce an apoptotic programme in the cell
Induces antibody dependent cytotoxicity

33
Q

What is the standard therapy of diffuse large B cell lymphoma?

A 
CHOP
cyclophosphamide
doxorubicin
vincristine
prednisone
34
Q

Give examples of targeted inhibitors

A

Ibrutinib
Idelalisib
ABT199
Imatinib

35
Q

What are the mechanisms of targeted inhibitors?

A 
Growth factor kinase inhibition
Apoptosis induction
DNA damage, response to inhibition
Epigenetic reprogramming
Telomerase inhibition
Redox modulation
Metabolic reprogramming
Proteasome inhibition
CSC trans-differentiation
Immune modulation
36
Q

Why are most of the new approvals of target agents in the haematology oncology space?

A

Much easier to access a haemato-oncological tumour using peripheral blood or through lymph node / bone marrow biopsy compared to pancreatic or liver tumour

37
Q

What is CML?

A

Cancer of haematopoietic stem cell

38
Q

What is the molecular pathogenesis of CML?

A

Monogenic
Philadelphia chromosome 9;22 translocation
Chronic phase of 4 years followed by blast phase

39
Q

What is Bcr-Abl tyrosine kinase?

A

Single molecular abnormality causing transformation of a haematopoietic progenitor into a malignant clone in CML

40
Q

How does imatinib work?

A

Starves Bcr-Abl tyrosine kinase of energy by binding to ATP binding pocket of aberrant tyrosine kinase. This switches off the activity of this kinase.

41
Q

Describe the resistance to imatinib

A

ABL kinase domain mutations prevent or reduce efficacy of binding of imatinib to ATP binding pocket
Increased amplification of BCR-ABL1
Clonal evolution - tumour is reliant on BCR-ABL
Drug efflux mechanisms - imatinib is a p glycoprotein substrate. Overexpression of p-gp on surface of CML blasts reduces bioavailability of imatinib

42
Q

Give examples of next generation tyrosine kinase inhibitors

A

Nilotinib
Dasatinib
Bosutinib
Ponatinib

43
Q

Described targeted therapy in NSCLC

A

Give gefitinib to those with mutated EGFR

Give crizotinib to those with genetic lesions that activate anapaestic lymphoma kinase

44
Q

How does gefitinib work?

A

EGFR kinase inhibitor

45
Q

How does crizotinib work?

A

oral anapaestic lymphoma kinase inhibitor

46
Q

What is vemurafenib used for?

A

Malignant melanoma

47
Q

How does vemurafenib work?

A

Switches off b-raf signal which switches off signalling downstream and interrupts b-raf / MEK / ERK pathway

48
Q

What is ibrutinib?

A

Example of targeted inhibitor important in CLL

Novel Bruton’s tyrosine kinase inhibitor

49
Q

What is ibrutinib used for?

A

CLL

Mantle cell lymphoma

50
Q

How does ibrutinib work?

A

Targets Bruton’s tyrosine kinase which is downstream of the B cell receptor
BTK inhibition switches of NFkB and NFAT and ERK signalling which arrests proliferation and reduces survival of malignant B cell

51
Q

Why is it important to target angiogenesis in solid tumours?

A

Solid tumour growth is limited by its ability to extract oxygen and nutrients from its microenvironment due to its vasculature or lack of blood supply
Tumour promotes neovascularisation allowing primary tumour to grow bigger and leading to metastatic disease

52
Q

Give examples of drugs targeting angiogenesis

A

Bevacizumab (avastin)

Perception (traztuzumab)

53
Q

How does bevacizumab work?

A

Blocks VEGF binding to VEGFR on surface of tumour which inhibits the angiogenic drive in tumour cells
Improves survival in colon, lung and renal cancer

54
Q

Describe HER-2

A

Human epidermal growth factor receptor 2
Overexpresed in 25% of breast cancers
Associated with more aggressive course of disease leading to metastases

55
Q

How does perception work?

A

Competitively inhibits EGF from binding to EGF receptor which blocks dimerisation of EGFR on surface of tumour cell. This stops signalling cascade downstream of EGF binding to EGFR

56
Q

What are the general principles of immunotherapy?

A

Immune system can recognise and react to cancers - immune surveillance hypothesis
Immune response against tumours is often dominated by regulation or tolerance
Some immune responses prompt cancer growth

57
Q

Describe potential immune cell responses to tumours

A

Macrophages recognise tumour specific antigens and engulf them leading to tumour eradication
B cells recognise tumour specific antigens via ligation of their B cell receptor leading to plasma cell production, humeral response and tumour specific antibody responses
B cells response requires CD4+ T helper cells
Potential that cytotoxic T-cells recognise tumour specific antigens presented to the on surface of tumour cell or in context of antigen presentation from B cell, macrophage or dendritic cell

58
Q

What immune responses promote tumour growth?

A

Tumour causes polarisation of CD4 T cells to produce Th2 cytokines (IL-4, IL-13)
Th2 cytokines cause macrophage polarisation to M2 macrophage which secrete iNOS and arg1 which actively repress cytotoxic T cells
Macrophages secrete VEGF, EGF and TGF beta which drives neoangiogenesis of tumour

59
Q

Describe neoantigens

A

Not normally present on non-malignant cells so no tolerance as they aren’t self
Produced by mutated genes that may be involved in oncogenesis or reflect genomic instability

60
Q

What are the 3 strategies being developed to harness hosts immune system to combat cancer?

A

Cancer vaccine production
Identify T cells that recognise tumour specific antigens and expand ex-vivo - CAR
Develop checkpoint control inhibitors

61
Q

Describe the PD-1 ligand in tumour cells

A

Tumours up regulate PDL-1 on their surface which encourages PDL1 ligation of PD-1 on affected T-cells leading to repressive signal to T cell
This stops T-cell mounting a cytotoxic response

62
Q

Describe the CTLA-4 molecule in tumour cells

A

Binds to and competes for co-stimulatory molecule expressed on APC - either CD80 or CD86
Competitive binding prevents CD80 or 86 binding to CD28 on T cell so T-cell won’t mount a cytotoxic response against tumour as it doesn’t have costimulation

63
Q

What are checkpoint blockade?

A

Strategies to block these checkpoint molecules and remove the breaks on the immune system
Repress CTLA-4 response using anti-CTLA-4 antibody

64
Q

Give an example of a anti-CTLA-4 antibody and its use

A

Ipilimumab for malignant melanoma

65
Q

Give examples of anti-PD-1 monoclonal antibodies

A

Pembrolizumab

Nivolumab

66
Q

What is the challenge of combining inhibitory checkpoints?

A

May increase toxicity

67
Q

Describe possible biomarkers of response vs resistance

A

Nature of cellular infiltrates around tumour
Expression of ligands for inhibitory receptors
Frequency of neoantigens in tumours from different patients
Frequency of tumour-specific exhausted T cells

68
Q

What are CAR-T?

A

Autologous T cells isolated from peripheral blood of patient and then expanded ex-vivo using CD3, CD28 Bs in combination with cytokines like IL-2
T-cells are transducer with a CAR then transferred back into patient

69
Q

Describe 1st generation CARs

A

Simple chimeric antigen receptors that spliced together a CD3 zeta chain with a single chain variable fragment that recognises the tumour antigen e.g. CD19

70
Q

Describe 2nd generation CARs

A

Incorporated co-stimulatory molecules into CAR

Once ligated, the CAR is fully activated so is con stimulated which drives signal to T cell to become cytotoxic

71
Q

Describe 3rd generation CARs

A

Incorporate multiple costimulatory molecules

72
Q

Describe 4th generation Cars

A

TRUCKS
Transcription factors e.g. NFAT attached to base of CAR.
Once engaged the receptor drives the activation of the transcription factor leading to cytokine release

73
Q

What are the limitations and challenges of CAR-T therapy?

A

Cytokine storm
Unclear how well it will work for solid tumours
Will tumour lose target antigen and develop resistance?
Technical challenges of producing genetically modified CAR-T cells for each patient
Exhaustion of transferred T cells
Increased risk of autoimmune reactions from endogenous T cell receptors

74
Q

Describe the exhaustion of transferred T cells and how this could be solved

A

Potential impact on longevity of response you might see from CAR-T cell
Patient T cells already show signs of increase immune cell raging
CRISPR editing of PD-1 from T-cells to reverse immune cell ageing or the exhaustion phenotype shown by these cells

302 Scientific basis of medicine (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions