Review for Final

Question 1

How is smoking related to cancer?

Answer 1

Causes a plethora of different cancers, the most important of which are lung cancer, breast and liver cancer. Most lung cancers are smoking related. Smoking produces chemicals such as benzo(a)pyrene which can lead to p53 loss, implicated in many checkpoints and apoptosis, increases cell migration and invasion.

Question 2

How is diet related to cancer?

Discuss the impacts of fruits.

Answer 2

• Fruits:
o Contain high levels of vitamin C – enhances the immune system and stimulates collagen formation to block off tumours and prevent metastases
o Rich in folate – important for DNA replication and repair, and for the co-enzyme SAM, important in methylation

Question 3

How is diet related to cancer?

Discruss the impacts of red and processed meats.

Answer 3

• Red and processed meats:
o Heme groups digested to form NOCs which can damage the cells lining the GI tract
o Nitrates/nitrites (preservatives) converted to NOCs through curing and digestion
o Barbecuing red meats can preduce HCAs and PAHs which can cause DNA damage

Question 4

How is diet related to cancer?

Discuss the impact of high fibre foods.

Answer 4

• High fibre foods:
o Fibre soaks up liquid in the GI tract and increase fecal mass
 Reduces contact time of harmful biliary acids and cancerous molecules to the GI
 Reduces carcinogen absorption
o Interacts with gut bacteria to produce an environmental unsuitable for tumour development

Question 5

How is diet related to cancer?

Discuss the impact of salt-preserved foods.

Answer 5

• Salt-preserved foods
o Cause inflammation of stomach lining – related to many cancers
o Can interact with and promote invasion of H. pylori

Question 6

How is candy related to cancer?

Answer 6

• Increased glucose present and circulating in the blood – can increase proliferation of cancer cells following the phenomena called the Warburg effect
• Phenomena in which cancer cells preferentially use glycolytic metabolism rather than oxidative phosphorylation
• Carbohydrate restriction may aid in the fight against cancer

Question 7

How are glucosinolates related to cancer?

Answer 7

• Populations that consume higher levels of raw cruciferous vegetables tend to have lower cancer incidences
• These vegetables contain folate, vitamin C and dietary fibres
• Low levels of sulphorophane, derived from broccoli can suppress oncogenic pathways and promote cytoprotective pathways
• Can activate the NRF2 pathway to activate NQ01, to reduce ROS which are cancer promoting
o Inhibits the inflammatory NF-kb pathway, implicated in many cancers and HDACs, which may promote loss of tumour suppressor function (p21, p53)

Question 8

How is alcohol consumption related to cancer?

Answer 8

• Excessive and chronic drinking has been linked to many GI-related cancers
• Metabolism of ethanol produces acetaldehyde, a type 1 carcinogen – induces inflammation and cell transromation
• Ethanol may also solubilize and aid in penetrance of other carcinogens in cigarette smoke
• May reduce folate absorption and raise estrogen levels

Question 9

How are tanning beds related to cancer?

Answer 9

UV radiation from indoor tanning beds is associated with an increased risk of melanoma and other skin cancers.
UV radiation can generate thymine dimers, which if not repaired, can become fixed in the genome and lead to cancer.

Question 10

How are disruptions in the circadian rhythm related to cancer?

Answer 10

• Electronic light can affect the SCN (suprachiasmatic nucleus) and disturb circadian regulation
o Similarly, night shift work and artificial light can interfere with melatonin release and cell cycle regulation
o Circadian rhythm genes may regulate the expression of genes implicated in cell growth

Question 11

How is absestos related to cancer?

Answer 11

• Asbestos exposure is related to a multitude of cancers, but the most important are pleural mesothelioma and lung cancer
• The risks of asbestos exposure are great, as they can produce hard to treat cancers and have a long latency period before symptoms arise – clinical diagnosis is often late when the cancer is highly aggressive and hard to treat
• Those at serious risk of developing mesothelioma are those exposed chronically and at high doses

Question 12

What is nanoparticle-mediated cancer therapy?

Answer 12

Nanoparticle-mediated cancer therapy is a novel approach using small entities to overcome the limitations of current cancer treatment options through specific and optimized drug delivery.
o Delivery system consist of: a targeting agent (specificity), apoptosis activating agent, carrier (contains the therapeutic agent

Question 13

What are the major limitations of nanoparticle-mediated cancer therapy?

Answer 13

o Limitations:
 May change the pharmacokinetic properties of drugs, limiting their effectiveness
 Short-lived nanoparticles (Ex: PLGA) may degrade before reaching targets
• Long-lived nanoparticles may persist and lead to adverse effects
 Many nanoparticles may instead localize in the liver and spleen
 High cost associated

Question 14

What is oncolytic viral therapy?

Answer 14

Oncolytic viral therapy is the use of genetically modified viruses to target cancer cells specificially.
• Viral-mediated therapies can be developed using attenuation or direct evolution. Attenuation involves genetically modifying genes to attenuate the virus, direct evolution involves placing selective pressures to design a virus with desired characteristic

Question 15

What are the main benefits of nanoparticles?

Answer 15

o Addresses the major limitation of both specificity and improving the delivery of cancer drugs to target sites.
o Can be employed to reduce systemic toxicity by targeting cytotoxic compounds to neoplastic tissues directly
o Can overcome P-glycoprotein-mediated resistance – a non-specific ATP driven export pump that contributes to MDR in many cancers
o Can be designed to circumvent opsonisation, can increase penetrance into difficult areas such as the brains through micelle development. Can deliver multiple drugs at once and can target tumours through pH changes (tumours are generally acidic).

Question 16

What are the main benefits of oncolytic viral therapy?

Answer 16

The main benefits of oncolytic viral therapy are that they produce less severe side effects than traditional treatments such as chemotherapy, can maximize response when combined with conventional treatmetns.

Question 17

What are the main limitations of oncolytic viral therapy?

Answer 17

• The main limitations to oncolytic viral therapy are that an immune response may limit its effectiveness, tend to have a lower response rate than chemotherapy, can attack non-cancerous cells, the risk of mutations are always possible and these methods are generally costly.

Question 18

What is immunotherapy, and what are the different facets of it?

Answer 18

Type of cancer treatment that utilizes a patient’s own immune system to destroy tumour cells.
1 - Monoclonal antibodies
2 - Immune checkpoint inhibitors
3 - Non-specific immune stimulation
4 - Cancer vaccines
5 - Car-T-cell therapy

Question 19

Describe monoclonal antibody cancer treatment.

Answer 19

Generally used as targeted therapy (ex: bevacizumab) to target specific abnormal proteins in cancer cells. These then increase the immune response towards these specific targets or directly block the abnormal proteins.

Question 20

Describe non-specific immune stimulation.

Answer 20

– do not target cancer cells specifically but increase the immune systemresponse towards cancer (interferons, interleukins, cytokines)

Question 21

Describe vaccination strategies.

Answer 21

exposes the body to antigens that are overexpressed by cancer cells (ex: mesothelin) to have the immune system target tumours.

Question 22

Describe immune checkpoint inhibitors.

Answer 22

bind to overexpressed PD-1/PLD1 to prevent cancer cells from circumventing T-cell mediated destruction

Question 23

Describe Car-T-cell therapy

Answer 23

involves the genetic manipulation of T-cells from a patient to express CARs through gene transfer methods to target cancer cells expressing specific antigens.
• Best for treating blood cancers and neuroblastoma

Question 24

What are the limitations of Car-T-cell therapy?

Answer 24

• Limitations:
o Poorly effective for solid tumours (Express certain antigens which restrict CAR-T cells from recognizing them)
o Side effects
 Cytokine release syndrome – develop flu-like symptoms and an overactive immune system – tend to benefit the most from this therapy
 Tumour lysis syndrome – contents of tumours are released into the bloodstream and can cause metabolic complications

Question 25

What are the limitations for immunotherapy?

Answer 25

 The optimal duration for immunotherapy is unknown
 Immune deregulation can lead to severe autoimmune reactions
 Treatments tend to be costly
 Tend to be limited in effectiveness for solid tumours