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4 - TC > Colorectal/Bowel Cancer 2 > Flashcards

Colorectal/Bowel Cancer 2 Flashcards

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1
Q

What are the types of targeted therapy?

A

monoclonal antibodies
immune checkpoint inhibitors

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2
Q

What are the different ways of making monoclonal antibodies?

A

Murine
- these are made from mouse proteins and the names of the treatments end in -OMAB.

Chimeric
- these proteins are a combination of part mouse and part human, and the names of the treatments end in - XIMAB

Humanized
- these are made from small parts of mouse proteins attached to human proteins and the names of the treatments end in - ZUMAB

Human
- these are fully human proteins, and the names of the treatments end in - UMAB.

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3
Q

What are the side effects of monoclonal antibodies? How can it be avoided?

A

Allergic reactions:
- chills, fevers, breathlessness and wheezing, itchy rash, changes in blood pressure

Pre-medicate with paracetamol, antihistamine and steroid to try prevent allergic reaction

If not life threatening - continue infusion at a slower rate

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4
Q

What is the mechanism of action of cetuximab?

A

is a chimeric immunoglobulin G (IgG) antibody that induces EGFR internalization and degradation once bound to the external domain of EGFR
- inhibits the growth and survival of EGFR-positive tumours.

also directs the innate immune system to attack tumour cells by a process called antibody-dependent cell-mediated cytotoxicity (ADCC)

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5
Q

What are the side effects of cetuximab?

A

Acneiform rash on the face, upper chest and back - consists of papules and pustules affecting the face and upper body

Hypomagnesemia
Nail changes - starts after 4-8 weeks. Resolves once stopped
Conjunctivitis
Hypersensitivity reactions

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6
Q

What is the mechanism of action of panitumumab?

A

is a fully humanized monoclonal antibody
- inhibits the epidermal growth factor receptor

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7
Q

What are the side effects of panitumumab?

A

Acneiform rash on the face, upper chest and back
Diarrhoea
Nausea or vomiting

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8
Q

What are the risks associated with murine-human chimeric antibodies?

A

murine-human chimeric antibodies might cause hypersensitivity reactions (3.5 to 7.5%)

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9
Q

What is the mechanism of action of bevacizumab?

A

is a humanized anti-VEGF monoclonal IgG1antibody

VEGF-A binds to VEGF Receptors (VEGRF) causing growth of blood vessels to the tumour, providing oxygen and nutritional support to the tumour
- bevacizumab binds to VEGF-A, preventing interaction with VEGFR, preventing angiogenesis and causes tumour death

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10
Q

What is the mechanism of action of VEGF-A?

A

VEGF-A binds to and activates both VEGFR-1 and VEGFR-2, promoting angiogenesis, vascular permeability, cell migration, and gene expression.

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11
Q

What are the side effects of bevacizumab?

A

Myelosuppression - neutropenia, thrombocytopenia
Delayed wound healing

Cardiovascular - hypertension

Bowel perforation and fistula

Blood clots
Proteinuria

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12
Q

What is the mechanism of action of nivolumab and pembrolizumab?

A

Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1)
- whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance.

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13
Q

What is the mechanism of action of ipilimumab?

A

is an anti-CTLA-4 antibody
- blocks cytotoxic T lymphocyte antigen-4 (CTLA-4)
- blocking CTLA-4 removes an inhibitory signal from reducing the activity of T lymphocytes

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14
Q

What are the side effects of pembrolizumab?

A

pneumonitis - is inflammation of the lungs
arthralgia - joint pain/stiffness
hepatic (liver) toxicities

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15
Q

What are the side effects of nivolumab?

A

endocrine toxicities - thyroid, pituitary, and adrenal glands

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16
Q

What are the side effects of ipilimumab?

A

skin, gastrointestinal and renal (kidney) toxicities

17
Q

What is the mechanism of action of trifluridine and tipiracil?

A

trifluridine (antiviral drug)
- is a thymidine-based nucleoside analogue
- is incorporated into viral DNA during replication and inhibits DNA synthesis

tipiracil
- is a thymidine phosphorylase inhibitor
- prevents rapid metabolism of trifluridine, increasing the bioavailability of trifluridine

18
Q

What are the side effects of trifluridine and tipiracil?

A

Myelosuppression
Diarrhoea, nausea and vomiting
Fatigue

19
Q

What is the mechanism of action of regorafenib?

A

orally-administered inhibitor of multiple kinase
- KIT, RAF-1 and REF (oncogenesis)
- VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-alpha, PDGFR-beta, FGFR-1 and FGFR-2 (angiogenic receptors)
- CSF-1R (tumour immunity)

20
Q

What is leucovorin? What is its function?

A

is also known as folinic acid
- is a folic acid analog/active metabolite of folic acid

counteracts the effects of methotrexate (folic acid antagonists)
- helps normal, healthy cells
- allows higher doses of methotrexate to be used

enhances the effects of fluoroupyrimidines
- increasing the binding of the drug to thymidylate synthase thus inhibiting DNA synthesis

21
Q

What is dose banding?

A

Doses grouped or rounded nearest mg or 10mg to standardised dosing

22
Q

What is targeted therapy?

A

a term for agents directed at unique biological features of cancers rather than agents that kill cells as they replicate, including both cancer cells and others.

23
Q

What does EGFR and VEGF stand for?

A

Epidermal growth factor receptor (EGFR)

Vascular endothelial growth factor (VEGF),

24
Q

What are immune checkpoints? What are immune check point inhibitors?

A

immune checkpoints are inhibitory regulators of the immune system
- stop immune responses
- are often overexpressed on tumour cells or on non-transformed cells within the tumour microenvironment and compromise the ability of the immune system to mount an effective anti-tumour response.

immune checkpoint inhibitors work by blocking checkpoint proteins from binding with their partner proteins
- this prevents the “off” signal from being sent, allowing the T cells to kill cancer cells.

25
Q

What is immune tolerance?

A

the process by which immune cells are made unresponsive to self-antigens (can recognise ‘self’ antigens) to prevent damage to healthy tissues.

26
Q

How do cancer cells remain hidden from immune response?

A

by the upregulation of programmed death ligand 1 (PD-L1) which are expressed on T cells
- it leads to the down regulation of effector functions

allows self tolerance to be maintained

27
Q

What are the common side effects of VEGF inhibitors?
- bevacizumab, ramucirumab

A

bleeding
GI perforation
arterial thromboembolism
impaired wound healing
proteinuria
hypertension

28
Q

What are the common side effects of regorafenib?

A

hand foot syndrome (palmar-plantar erythrodysesthesia)
rash
fatigue
diarrhoea

29
Q

What are the side effects of EGFR inhibition?
- cetuximab, panitumumab

A

acneiform rash
paronychial infections, skin fissures
infusion related hypersensitivity, allergic reaction
mucositis
hypomagnesia

30
Q

What are the side effects of immune checkpoint inhibitors?
- pembrolizumab, nivolumab

A

immune mediated inflammation of any organ
- endocrine glands, skin, liver, GIT

fatal pneumonitis

31
Q

What are the side effects of BRAF inhibition?
- vemurafenib, encorafenib

A

fatigue
rash/skin toxicity
diarrhoea

32
Q

What is the mechanism of action trastuzumab?

A

monoclonal antibody against human epidermal growth factor receptor 2 (HER2)

binds to an extracellular domain of this receptor and inhibits HER2 homodimerization, thereby preventing HER2-mediated signaling
- stops cell growth and division

4 - TC (39 decks)

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