Brainscape's Knowledge GenomeTM

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


See full index

Cancer > Cancer 9. Biological Basis for Cancer Therapy > Flashcards

Cancer 9. Biological Basis for Cancer Therapy Flashcards

1
Q

What are the mosy common cancers worldwide?

A
  • Lung
  • Breast
  • Bowel
  • Prostate
  • Stomach
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the main anti-cancer modalities?

A
  • Surgery
  • Radiotherapy
  • Chemotherapy
  • Immunotherapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the types of genetic mutation that cause cancer?

A
  • Chromosome translocation
  • Gene amplification (copy number variation)
  • Point mutations within promoter or enhancer regions of the genes
  • Deletions or insertions
  • Epigenetic alterations to gene expression
  • Can be inherited
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name the types of systemic therapy.

A
  • Cytotoxic Chemotherapy
    • ​Alkylating agents
    • Antimetabolites
    • Anthracyclines
    • Vinca alkaloids and taxanes
    • Topoisomerase inhibitors
  • Targeted Therapies
    • ​Small Molecule Therapies
    • Monoclonal antibodies
  • Cytotoxic drugs ‘select’ rapidly dividing cells by targeting their structures (mostly DNA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

When would cytotoxic chemotherapy be used and how is it administered?

A
  • Given IV or occasionally orally
  • It works systemically
  • Non-targeted - it affects all rapidly dividing cells in the body e.g. hair and intestinal epithelium
  • Different times at which it can be used:
    • Post operatively = adjuvant
    • Pre-operatively = neoadjuvant
    • As a monotherapy or in combination
    • With curative or palliative intent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How do alkylating agents work?

A
  • These add alkyl (CNH2N+1) groups to guanine residues in DNA
  • It then cross-links DNA strands and prevents DNA from uncoiling at replication
  • It then triggers apoptosis (via a DNA checkpoint pathway)
  • It encourages mis-pairing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How do Pseudo-alkylating agents work?

A
  • These add platinum to guanine residues in DNA
  • It triggers the same mechanism of death as alkylating agents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Name alkylating agents.

A
  • Chlorambucil
  • Cyclophosphamide
  • Dacarbazine
  • Temozolomide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Name pseudo-alkylating agents.

A
  • Carboplatin
  • Cisplatin – binds to Guanine residues in DNA –> causes intra or inter cross-links being formed
  • Oxaliplatin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the side effects of alkylating and pseudo-alkylating agents?

A
  • Hair loss (not carboplatin)
  • Nephrotoxicity
  • Neurotoxicity
  • Ototoxicity (platins) - ears
  • Nausea
  • Vomiting
  • Diarrhoea
  • Immunosuppression
  • Tiredness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How to anti-metabolites work?

A
  • These masquerade as purine or pyrimidine residues leading to the inhibition of DNA synthesis, breaking of the double strand of the DNA and apoptosis.
  • Anti-metabolites can be purine analogues (adenine or guanine) or pyrimidine analogues (thymine/uracil and cytosine)
  • They can also be folate antagonists (these inhibit dihydrofolate reductase, which is required to make folic acid, an important building block of all nucleic acids (especially thymine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Name anti-metabolites.

A
  • Methotrexate
  • 6-mercaptopurine
  • Fludarabine (purine)
  • 5-fluorouracil
  • Capecitabine
  • Gemcitabine (pyrimidine) - causes deamination
    • Used in lung, pancreatic and ovarian cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the side effects of anti-metabolites?

A
  • Hair loss (alopecia) - not 5-fluorouracil or capecitabine
  • Bone marrow suppression causing anaemia, neutropenia and thrombocytopenia
  • Increased risk of neutropenic sepsis (and death) or bleeding
  • Nausea and vomiting (leading to dehydration)
  • Mucositis and diarrhoea
  • Palmar-plantar erythrodysesthesia (PPE)
  • Fatigue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do anthracyclines work?

A
  • Inhibit transcription and replication by intercalating (i.e. inserting between) nucleotides within the DNA/RNA strand
  • They also block DNA repair (mutagenic)
  • They create DNA-damaging and cell membrane damaging oxygen free radicals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Name examples of anthracyclines.

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

What are the side effects of anthracyclines?

A
  • Cardiac toxicity (arrhythmias, heart failure) - probably due to damage induced by free radicals
  • Alopecia
  • Neutropenia
  • Nausea
  • Vomiting
  • Fatigue
  • Skin changes
  • Red urine (doxorubicin = ‘the red devil’)
17
Q

How do vinca alkaloids and taxanes work?

A

They work by inhibiting the assembly (vinca alkaloids) or disassembly (taxanes) of MITOTIC MICROTUBULES causing dividing cells to undergo mitotic arrest

18
Q

What are the side effects of microtubule targetting drugs (i.e. vinca alkaloids and taxanes)?

A
  • Nerve damage: peripheral neuropathy, autonomic neuropathy
  • Hair loss
  • Nausea
  • Vomiting
  • Bone marrow suppression (neutropenia, anaemia etc.)
  • Arthralgia (severe pain in a joint without swelling or other signs of arthritis)
  • Allergy
19
Q

How do topoisomerase inhibitors work?

A
  • Topoisomerases are responsible for the uncoiling of DNA - they prevent DNA replication and transcription
  • They induce temporary single strand (topo1) or double strand (topo2) breaks in the phosphodiester backbone of DNA
  • They protect the free ends of DNA from aberrant recombination events
  • Topoisomerase inhibitors have anti-topoisomerase effects through their action on DNA
  • Specific topoisomerase inhibitors alter the binding of the complex to DNA and allow permanent DNA breaks
20
Q

Name examples of topoisomerase inhibitors.

A
  • Topotecan (topo1)
  • Irinotecan (topo1)
  • Etoposide (topo2)
21
Q

What are the side effects of topoisomerase inhibitors?

A
  • Irinotecan = acute cholinergic type syndrome (diarrhoea, abdominal cramps, diaphoresis (sweating) - they are therefore given atropine)
  • Hair loss
  • Nausea
  • Vomiting
  • Fatigue
  • Bone marrow suppression
22
Q

What are the resistance mechanisms by which a cell can survive chemotherapy

A
23
Q

What are the 6 or 10 hallmarks of cancer?

A

SPINAP

  • Self Sufficient
  • Pro-invasive and metastatic
  • Insensitive to anti-growth signals
  • Non-senescent
  • Anti-apoptotic
  • Pro-angiogenic

DIE U

  • Dysregulated metabolism
  • Evades the immune system
  • Unstable DNA
  • *I**nflammation
24
Q

Name receptors that are overexpressed in cancer.

A
  • HER2- amplified and over-expressed in 25% of breast cancers
  • EGFR- over-expressed in breast and colorectal cancer
  • PDGFR- glioma (brain cancer)

These are all growth factor receptors so over-expression will lead to an upregulation of the kinase cascade and signal amplification

25
Q

Which ligand is over-expressed in cancer?

A

VEGF - prostate, kidney and breast cancer

This also leads to upregulation of the kinase cascade and signal amplifications

26
Q

What receptors are constitutively (ligand independently) activated?

A
  • EGFR- lung cancer
  • FGFR- head and neck cancers, myeloma
27
Q

Explain the meaning behind suffixes of monoclonal antibodies.

A
28
Q

How do monoclonal antibodies work?

A
  • Monoclonal antibodies target the extracellular component of the receptor
  • The monoclonal antibodies:
    • Neutralise the ligand
    • Prevent receptor dimerisation
    • Cause internalisation of the receptor
  • They also activate Fcgamma-receptor-dependent phagocytosis or cytolysis induced complement-dependent cytotoxicity (CDC) or antibody-dependent cellular cytotoxicity (ADCC)
29
Q

Name example of monoclonal antibodies.

A
  • Bevacizumab binds and neutralises VEGF - this improves survival in colorectal cancer
  • Cetuximab target EGFR
30
Q

How do small molecule inhibitors work.

A
  • These bind to the kinase domain within the cytoplasm and block autophosphorylation and downstream signalling
31
Q

How does Glivec work?

A
  • Glivec is a small molecule inhibitor
  • It is used to treat chronic myeloid leukaemia
  • In CML, there is a chromosomal translocation forming a fusion protein Bcr-abl –> an enzyme that over produces white cells.
  • Glives targets the ATP binding region within the kinase domain
  • It inhibits the kinase activity of ABL1
32
Q

What are the advantages and disadvantages of targeted therapies (i.e. monoclonal antibodies and small molecules)?

A
  • However, one big problem is RESISTANCE
33
Q

What are resistance mechanisms against targeted therapies?

A
  • Mutations in ATP-binding domain (e.g. BCR-Abl fusion gene and ALK gene, targeted by Glivec and crizotinib respectively)
  • Intrinsic resistance (herceptin is effective in 85% of HER2+ breast cancers, suggesting other driving pathways)
  • Intragenic mutations
  • Upregulation of downstream of parallel pathways (that lead to cell proliferation)
34
Q

How do anti-sense oligonucleotides work?

A
  • Single-stranded, chemically modified DNA-like molecule 17-22 nucleotides in length
  • This complementary nucleic acid hybridisation to the target gene hinders translation of specific mRNA
  • It recruits RNase H to cleave target mRNA
  • This is good for ‘undruggable’ targets
35
Q

How does RNA interference work?

A
  • Single-stranded complementary RNA
  • This has lagged behind anti-sense technology - especially in cancer therapy
  • Compounds have to be packagedto prevent degradation (nanotherapeutics)
  • CALAA-01 targeted to M2 subunit of ribonucleotide reductase (phase 1 clinical trials in cancer at the moment - results are awaited)
36
Q

Name a few successful drugs in cancer treatment.

A
  • B-Raf inhibitor = VEMURAFENIB
    • ​Side effects: arthralgia, skin rash, photosensitivity
  • Immune modulation by programmed cell death -
    • binding of the ligand PDL1 to the PD-1 receptor will mean that the body’s T cells can no longer recognise tumour cells as foreign__​
    • So if either the PDL1 ligand or the PD-1 receptor are blocked, the immune system will be stimulated
    • NIVOLUMAB - anti-PD1 antibody
37
Q

What are new therapeutic avenues for cancer?

A

Cancer (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions