Colorectal/Bowel Cancer 2 Flashcards
What are the types of targeted therapy?
monoclonal antibodies
immune checkpoint inhibitors
What are the different ways of making monoclonal antibodies?
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.
What are the side effects of monoclonal antibodies? How can it be avoided?
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
What is the mechanism of action of cetuximab?
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)
What are the side effects of cetuximab?
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
What is the mechanism of action of panitumumab?
is a fully humanized monoclonal antibody
- inhibits the epidermal growth factor receptor
What are the side effects of panitumumab?
Acneiform rash on the face, upper chest and back
Diarrhoea
Nausea or vomiting
What are the risks associated with murine-human chimeric antibodies?
murine-human chimeric antibodies might cause hypersensitivity reactions (3.5 to 7.5%)
What is the mechanism of action of bevacizumab?
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
What is the mechanism of action of VEGF-A?
VEGF-A binds to and activates both VEGFR-1 and VEGFR-2, promoting angiogenesis, vascular permeability, cell migration, and gene expression.
What are the side effects of bevacizumab?
Myelosuppression - neutropenia, thrombocytopenia
Delayed wound healing
Cardiovascular - hypertension
Bowel perforation and fistula
Blood clots
Proteinuria
What is the mechanism of action of nivolumab and pembrolizumab?
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.
What is the mechanism of action of ipilimumab?
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
What are the side effects of pembrolizumab?
pneumonitis - is inflammation of the lungs
arthralgia - joint pain/stiffness
hepatic (liver) toxicities
What are the side effects of nivolumab?
endocrine toxicities - thyroid, pituitary, and adrenal glands