Oncology Flashcards
What is cancer? (2 points)
- disease characterised by uncontrolled, unregulated growth of abnormal forms of the body’s own cells.
- these cells invade surrounding tissues and migrate to other parts of the body
What are the 4 main characteristics of cancer cells that distinguish them from normal cells?
- uncontrolled growth
- loss of function
- invasiveness
- metastases
What are the 4 main types of tumour types?
- carcinoma (skin or tissues lining organs)
- sarcoma (bone, muscle, blood vessels, tissues)
- leukaemia (bone marrow)
- Lymphoma (immune system)
What are the 5 approaches in cancer treatment?
- chemotherapy
- surgery
- radiotherapy
- hormone therapy
- immune therapy
What is the purpose of chemo and radiation?
-to kill tumour cells as these cells are more susceptible to the actions of these drugs
What are the problems associated with chemotherapy? (6 points)
Side effects which arise from parameters such as
- formulation factors (solubilisers)
- PK variability
- non-selective toxicity
- poor drug solubility and stability
- drug resistance
- lack of oral chemotherapy
What are the attempts of newer chemotherapy formulations focussing on? (2 points)
- efforts to kill cancer cells by more specific targeting while sparing normal cells
- to achieve this, the focus is on development of novel drug delivery carriers for both existing and new drugs
What are the roles of drug delivery systems (4 points)
- reduced side effect of chemo agents
- enabling new and better chemotherapeutics regimen using existing pharmaceuticals
- facilitate cancer prevention
- pain management assoc with caner progression and chemo
What are the different drug delivery strategies? (8 points)
- chemotherapy wafers
- patches
- osmotic pumps
- PEGylated liposomes
- liposomes
- microspheres
- polymer-drug conjugates
- microchips
What are nanoparticulate drug delivery carriers? (2 points)
- NPs are engineered, constructed systems measured in nm size.
- made of polymers/polysaccharides of different nature
What are the advantages of NP carrier systems to tumour tissues? (3 points)
-enhanced permeation through tumour due to leaky, abnormal vasculature of cancer site (small particle size
What are the limitations of NP delivery?
-NPs will be taken up by liver, spleen and other parts of the reticulo-endothelium system, depending on their surface characteristics and particle size
What are the two ways of targeting NP to tumour tissues?
- passive targeting
- active targeting
What is passive targeting? (2 points)
- limited to RES uptake after injection of NP
- this limits the effective delivery of anticancer drug-loaded NPs to cancer cells
What is active targeting?
-this involves drug delivery to a specific site based on molecular recognition
What are the 5 strategies to improve active targeting to avoid RES?
- PEGylation
- construction of particles with hydrophilic surface
- couple a ligand to the NP
- use magnetic field
- size reduction
How does PEGylation improve active targeting?
-adds polyethylene glycol over surface of NP so it is not recognised by the RES
How does a hydrophlic surface help improve active targeting to avoid RES? (2 points)
- hydrophilic surface either by construction or coating with surfactant creates cloud of chains at the particle surface
- this repels plasma proteins and prevents opsonisation [cloud effect]
How does coupling a ligand to a NP improve active targeting to avoid RES?
- the ligand can interact with its receptor at the target cell site
- e.g. binding of folate to pyglayted particles for interaction with folate receptor
How does magnetic field help to improve active targeting to avoid RES?
-Magnetic field can be used to orient the NP towards a magnetic field created at the tumour site
What are the 5 types of nanoparticles?
- dendrimers
- nanospheres
- nanocapsules
- fullerenes and nanotubes
- liposomes
What are dendrimers?
-regularly branched 3D tree like structures with multifunctional central core
What are nanospheres?
-spherical structures composed of matrix system where drug is distributed by entrapment, attachment or encapsulation
What are nanocapsules?
-vesicular systems with central cavity/core
which is surrounded by an outer shell polymeric membrane
What are fullerenes/nanotubes?
-family of molecules composed of carbon in the form of hollow sphere or ellipsoid tube
What are liposomes?
-structures of closed vesicles composed of lipid layers, classified according to the number of lipid layers as either unilaminar or multilaminar
What are examples of nanoparticles in clinical use? (3 points)
- Paclitaxel
- doxorubicin
- Doxil
What is the Paclitaxel NP formulation?
-Paclitaxel is incorporated in poly(lactic-Co-glycoli) acid nanoparticles
What is the doxorubicin NP formulation?
-doxorubicin conjugated with dextran incorporated in chitosan nanoparticles
What is the Doxil NP formulation? (6 points)
- Pegylated liposomal doxorubicin.
- small particles (
How are wafers used as DD cariers?5 points
- Biocompatible polyanhidride polymer
- rate of degradation well controlled with no residual foreign body
- achieves near 0 order release
- protects drug from hydrolytic cleavage
- e.g. Gliadel wafers (implant)
What is a new approach to cancer treatment?
-gene therapy
What is gene therapy? (2 points)
- Cancer in most cases is genetic disease caused by genetic aberrations and subsequent gene defects
- Gene therapy introduces new genes in cells to replace a missing/defective gene
What are the strategies for cancer gene therapy? (3 points)
- introduction or reactivation of tumour suppressor genes
- inactivation of oncogenes
- introduction of genes that lead to expression of enzymes, proteins or that activate immune systems
How will gene therapy avoid transduction of all cells in the body?
-it must be targeted to cells of interest
How can gene therapy be targeted? (3 points)
- use naked DNA by direct injection to tumour site
- use of viral vectors
- use of non viral vectors
What are the advantages and disadvantages of injecting free DNA? (4 points)
+produces high levels of gene expression
+simple method
-limited to tissues easily accessible by direct inj. such as skin and muscles
-unsuitable for systemic delivery due to serum nucelase
What are viral vectors? (3 points)
- viruses are capable of transferring their genetic material into cells
- viral vectors are biological systems which have been modified to eliminate toxcity but maintain ability gene transfer
- e.g. retrovirus, adenovirus, herpes simplex virus
What are the advantages and disadvantages with using viral vectors? (4 points)
+effective in achieving high efficiency for gene delivery and expression
- low safety
- immunogenicity
- high cost
How can non-viral vectors be used in gene transfer? (2 points)
- these are delivery systems of cationic nature consisting of polymers and lipids
- e.g. PEI, chitosan, dendrimers, coated cationic liposomes
What are the advantage and disadvantages of non-viral vectors?
+suitable for large scale production
+low immunogenic response
+has possibility of selected modification and capacity to carry large inserts
-transfection efficiency is lower than that for viral vector
