Cancer 2 Flashcards
Name a drug that targets EGRF mutation [2]
Gefitinib or erlotinib
Tyrosine kinase receptors:
Name 4 key antibody targets that are GF receptors and / ligands
Epidermal growth factor receptor (EGFR)
HER2 (no ligand)
HER2/3 (ligand: HER2 can bind to HER3 – activates different pathway)
Vascular endothelial growth factor (VEGF)
State difference in antibody and small molecule kinase inhibitors
Antibodies:
* high selectivity
* targets are often restricted to the cell surface
* require intravenous or subcutaneous dosing because of their large molecular weight
* Can be conjugated to cytoxic drugs
Small molecule kinase inhibitors:
* vary in selectivity
* Oral
* Bind- ATP binding sites
* Can potentially bind a wider range of extracellular and intracellular targets (> one kinase)
Describe the mechanism of antibodies [2] and SMKI [1]
Antibody:
* Produce antibodies that target extracellular part of tyrosine kinase receptor
* Inhibits ligand binding or causes the ligand to bind in an area that doesn’t cause dimerization
SMKI:
* Binds to ATP binding pocket & intracellular-P cant occur
State the overall three mechanisms of monoclonal antibodies [3]
Killing tumour cell directly
Killing tumour cells via an immune-mediated mechanism
Vascular or stromal ablation: VEGF antagonsim
Describe mechansim of trastuzumab emtansine (Kadcycla)?
Kadycycla is formed from the conjugate binding of Herceptin with DM1, which is an anti-microtubule agent
Drug is taken up by lysosome.
Within the lysosome: herceptin and DM1 dissociate and are released into cell
DM1 attacks cell tubule
What is first line treatment of HER2-positive breast cancer? [3]
Pertuzumab (HER2/HER3 blocker), in combination with trastuzumab (HER2 blocker) and docetaxel
What is second line treatment of HER2-positive breast cancer? [2]
Trastuzumab - emtansine (Kadcycla)
What is third line treatment of HER2-positive breast cancer? [2]
Trastuzumab-deruxtecan
Describe overall mechanism of Small Molecule Tyrosine Kinase Inhibitors (e.g. Tarceva)
Tarceva has similar structure to ATP
Binds to ATP binding pocket in the cell membrane causes competitive inhibition in ATP binding pocket-inhibit function of kinases
Explain what a second generation tyrosine kinase inhibitor is [1]
Name a second gen tyrosine kinase inhibitor for EGFR in NSCLC [1]
Drug for the new mutation of the tyrosine kinase receptor
Mutations associated with drug resistance to erlotinib so Osimertinib prescribed (fits the new ATP binding site)
Monoclonal antibodies and cancer therapy mechanisms:
Explain how killing tumour cells directly via monoclonal antibodies works [4]
- Inhibit ligand binding
- Or possible delivery of toxic payload
- Signalling blocked
- Apoptosis induced
Monoclonal antibodies and cancer therapy mechanisms:
Explain how killing tumour cells directly via an immune-mediated mechanism works [3]
- Induction of phagocytosis
- Complement-dependent cytotoxicity (CDC)
- Antibody-dependent cell cytotoxicity (ADCC)
Monoclonal antibodies and cancer therapy mechanisms:
Explain how killing tumour cells directly via vascular or stromal ablation works [1]
VEGF antagonism
Cetuximab inhibits which receptor:
HER2
HER2/HER3
EGFR
VEGF
Cetuximab inhibits which receptor:
HER2
HER2/HER3
EGFR
VEGF
Name a small molecule tyrosine kinase Inhibitors [1]
Tarceva
(Erlotinib)
Name three pathways that are targets for kinase inhibitors [3]
- Transcription
- Receptor tyrosine kinase signalling
- Proto oncogenes
How does HER2 resistance occur?
As tumours develop they acquire mutations.
With HER2: becomes truncated: extracellular part becomes truncated.
As a result, kinase activity is switched off (doesn’t need receptor activation to switch on intracellular pathway).
As a result Herceptin stops working as there is no binding sit
Name a AE of targeting VEGF [1] and EGFR [1]
VEGF: High blood pressure
EGFR: Slow wound healing and blood clotting
This rash comes from which cancer drug? [1]
Trastuzumab - rash
Describe the effects of HER2 on cardiomyocytes [1]
HER2 inhibits cardiomyocyte apoptosis [1]
Describe the cardiotoxic effects of Trastuzamab [2]
Inhibits HER2 cardiomyocyte apoptosis
Get a decline in left ventricular function AND congestive heart failure
Need regular cardiac monitoring
Explain a draw back of using antibodies as a targeted therapy [1]
Cannot pass the cell membrane and must be given IV
What type of radiotherapy would be used for lesions requiring full dose to the surface (skin) to max 2-3cm depth meaningful treatment such as to the following areas:
Eyes
Skin lesions
Post op skin lesions
Benign conditions
Superficial KV photons
Only penetrates a few mm (good for skin lesions)
LINAC Electron based treatments are used for lesions in where in body? [4]
Lesions requiring dose closer to the skin
Lesions on the skin – using bolus
Skin
Lymph node regions
Where would LINAC based treatments: MV photons (mega voltage) [1]
What is dosing regimen like? [1]
More penetrative treatment and dose at depth
High dose radical treatments are fractionated (broken up into smaller daily treatments) to deliver treatment safely and avoid damage to adjacent normal tissues/organs
What are stereotactic radiotherapy treatments? [1]
Higher dose treatments: smaller margins, closer monitoring
Often considered ‘radiosurgery’, very targeted
What is brachytherapy?
Using radioactive seed or implant to deliver targeted radiotherapy
What is the most common platinum agent used for chemotherapy in concomitant therapy? [1]
cisplatin given with radiotherapy for SCC- acts as a radiosensitiser in many cases
Which type of cancers can chemotherapy act as curative treatment for? [1]
Germ cell tumours (testicular, ovarian, mediastinal)
What is neo-adjuvent chemotherapy? [1]
Name a cancer that is common for [1]
Chemotherapy given prior to surgery / radiation: improves patient fitness and operations are smaller / less invasive
Ovarian cancer
What is adjuvent chemotherapy? [1]
Give an example of a cancer that its used on [1]
Given after radiation / surgery: eradicates evasive cancers
Breast cancer
Give 3 examples of alkylating agent chemotherapy [3]
Cyclophosphamide
Ifosfamide
Busulfan
Name a common AE of alkylating agent [1]
hemorrhagic cystitis: condition in which the lining of the bladder becomes inflamed and starts to bleed.
Types of chemotherapy
Describe MoA of platinum agents [1]
Primary mode of cell death is damage to cellular DNA by the development of covalent adducts
Give 3 examples of planitum agent chemotherapies [3]
Carboplatin
Cisplatin
Oxaliplatin
Types of chemotherapy
Describe MoA of anti-metabolites [2]
Most antimetabolites are structural analogs of molecules that are normally involved in the process of cell growth and division
They are incorporated into DNA and/or RNA and interfere with synthesis by conveying false messages
Give an example of anti-metabolites [1]
Methotrexate (derivate of folic acid)
Types of chemotherapy
Describe MoA of TOPOISOMERASE INHIBITORS [1]
DNA Topoisomerases (I & II) are essential enzymes that regulate the topological state of DNA during cellular processes such as replication, transcription and chromatin remodeling.
Name examples of two topoisomerase I and II [4]
Topoisomerase-I
* Irinotecan
* Topotecan
Topoisomerase-II
* Doxorubicin
* Epirubicin
Which of the following is cardiotoxic and cause dilated cardiomyopathy
- Irinotecan
- Topotecan
- Doxorubicin
- Epirubicin
- Irinotecan
- Topotecan
- Doxorubicin
- Epirubicin
Types of chemotherapy
Describe MoA of tubulin active agents [1]
What are the two types? [2]
Give two examples of each type [4]
Microtubules are a core component of mitotic spindle that separates chromosomes during eukaryotic cell division
Vinca Alkaloids prevent assembly of microtubules and at higher doses inhibit mitotic spindle formation:
* Vinblastine
* Vincristine
Taxanes bind to microtubules; promotes assembly into microtubles and inhibits disassembly
* Paclitaxel
* Docetaxel
Name the 4 misellaneous chemotherapy drugs and explain their MoA [4]
MISCELLANEOUS
Bleomycin
Mixture of cytotoxic glycopeptide antibiotics isolated from the fungus streptomyces verticillus that possess both anti-tumour and anti-bacterial properties however exact mechanism of action is unknown
Actinomycin-D
Another antibiotic from streptomyces parvullus; it exerts cytotoxic effects by intercalation between guanine-cytosine base pairs with inhibition of the synthesis of messenger RNA
L-Asparaginase
Contains the enzyme L-asparaginase originally isolated from escherichia coli; anti-tumour effect results from rapid and complete depletion of asparagine in the bloodstream and extracellular space which deprives tumour cells of the required amino acids and inhibits protein synthesis
Trabectedin
Derived from ecteinascidia turbinata; binds to the minor groove of DNA, bending the helix towards the major groove, which leads to interference with the intracellular transcription pathways and DNA-repair pathways
Name drugs that target each stage of the cell cycle (G1 / S / G2 / M)
* G1: vinblastine
* S: Methotrexate, 6-Mercaptopurine, 5-fluorouracil
* G2: Bleomycin, etoposide, topotecan, daunorubicin
* M: vincristine, vinblastine, paclitaxel, docetaxel
Name some general side effects of chemotherapy [7]
Nausea, vomiting, mouth ulcers, change in taste, diarrhea, constipation
Fatigue
Bleeding, bruising and risk of life-threatening infection
Rash, skin changes, nail changes
Change in liver function, cardiac function, lung function, renal function
Neuropathy, tinnitus
Early menopause, loss of libido and infertility
Blood clots
Hair loss
Allergic reaction
Which chemotherapy drug would cause Palmar-Planter Erythrodysesthesia?
Capecitabine
Bleomycin
Doxorubicin
Imatinib
Which chemotherapy drug would cause Palmar-Planter Erythrodysesthesia?
Capecitabine
Bleomycin
Doxorubicin
Imatinib
Which chemotherapy drug would cause Pulmonary Fibrosis?
Capecitabine
Bleomycin
Doxorubicin
Imatinib
Which chemotherapy drug would cause Pulmonary Fibrosis?
Capecitabine
Bleomycin
Doxorubicin
Imatinib
Which chemotherapy drug would cause Raspberry Urine?
Capecitabine
Bleomycin
Doxorubicin
Imatinib
Which chemotherapy drug would cause Raspberry Urine?
Capecitabine
Bleomycin
Doxorubicin
Imatinib
Which chemotherapy drug would cause Peri-Orbital Oedema?
Capecitabine
Bleomycin
Doxorubicin
Imatinib
Which chemotherapy drug would cause Peri-Orbital Oedema?
Capecitabine
Bleomycin
Doxorubicin
Imatinib
Which chemotherapy drug would cause Flagellate Erythema ?
Capecitabine
Bleomycin
Doxorubicin
Imatinib
Which chemotherapy drug would cause Flagellate Erythema ?
Capecitabine
Bleomycin
Doxorubicin
Imatinib
