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Flashcards in Therapeutic Options Deck (31):

Prevention methods

- Diet
- Stop people smoking
- Screening
- Genetics
- Medication


Diet in prevention

- Inconsistent evidence, lots of confounding factors
- CRC is probably linked with red meat consumption
- Breast cancer: probably a link with saturated fat intake
- Physical activity decreases risk
- Current advice: 5 or more portions of fruits and vegetables a day, avoid obesity, take regular exercise 30 minutes a day


Screening in prevention

- Risks are involved with screening, so you may cause harm
- E.g. breast screening might perform a mammectomy on a patient who has a lump that may never turn into cancer
- High quality evidence for smear tests, CRC (faecal occult blood test), breast cancer
- Controversial: PSA blood test for prostate cancer, MR/CR or breath test for lung cancer


Genetics in prevention

- CRC and familial adenomatous polyposis coli (FAP)
- Autosomal dominant
- Screening families for APC mutations
- Regular colonoscopy
- Offer panprotocolectomy when adenomas found
- Breast cancer: BRCA1, BRCA2


Medication in prevention

- Also known as chemo-prevention
- More controversial


Primary medication in prevention

- Oesophageal cancer: high rate in parts of chine, they tried anti-oxidant supplements but there was no benefit
- Breast cancer: at risk women, prophylactic tamoxifen (higher risk of getting endometrial cancer with this)


Secondary medication in prevention

- Previous head and neck or lung cancers
- Give anti-oxidant supplements
- No benefit



- Local or regional treatment: surgery or radiotherapy
- Systematic therapy: hormonal, chemo, immunotherapy


Surgery treatment of cancers

- Need anatomical clearance
- Get all the cancer out
- 50% of cancers cured this way


Radiotherapy treatment of cancers

- Needs anatomical coverage
- Can treat inoperable lesions
- Can treat things you can't remove and/or allow surgery to be possible
- Approx. 40% of cancers cured by this
- Can be combined with chemo: anal cancer, rectal cancer, oesophageal cancer
- Palliation
- Maintain function and/or appearance



- Reduce pain
- Bleeding
- Swollen limbs
- Aims to improve symptoms


Maintaining function with radiotherapy

- Gullet cancer, you can't remove it so you need to maintain function
- Ear lesion, you can keep your ear with radiation therapy


5R's of radiobiology

- Radiosensitivity
- Repair
- Re-population
- Re-oxygenation
- Re-assortment



- How sensitive the tumour is going to be to treatment
- Can anticipate outcome
- Certain drugs have been proven to increase radiosensitivity



- Radiation damages cells to a sublethal level, often the cell pathways repair themselves have been suppressed in malignant tumours
- The degree of suppression will affect the repair half-life and how effective the treatment is



- Cells will all be in different parts of the cell cycle
- S phase: typically radioresistant
- Late in G2 or M phase are relatively sensitive
- Idea is you catch them at some point in the cycle when they're in a more sensitive phase



- Tumours can be acutely or chronically hypoxic, this makes the resistant to radiation
- The aim of radiation is to make them oxic as oxic cells can be killed



- Cells are in a cycle and you catch some cells at different stages, some are sensitive to radiotherapy and some aren't
- G2 and M are good, late S isn't so good


Systemic therapy

- Beneficial for widespread disease
- Can result in widespread toxicity
- Palliation in about 50% of cancers
- Potential to be very specific
- Therapeutic index: aim is to have the anti-tumour effect curve and normal tissue toxicity as far apart as possible. Separates side effects and anti-tumour effects


Hormonal therapy

- 'Specific' or 'targeted' therapy
- Benefits in breast cancer (oestrogen receptor positive and tamoxifen) and prostate cancer (luteinising hormone-releasing hormone antagonists)
- Trials in prevention for high risk groups e.g. tamoxifen


What are the 4 basic types of chemotherapy?

- Curative
- Palliative
- Adjuvant
- Neoadjuvant


Curative chemotherapy

- Only about 3% of cancers, testicular, lymphomas
- Can be used with radiotherapy
- Important to use biomarkers to see what genes the tumours have, assess treatment methods


Palliative therapy

- Accounts for around 50% of chemotherapy
- Aim is to relieve symptoms



- When there is no longer evidence of pathology
- Can reduce risk of recurrence. Based on population statistics rather than the individual



- Aim is to improve survival and reduce morbidity
- Precedes surgery or radiotherapy
- Before people have surgery to see how the cancer is going to behave and decide whether to do local or systematic therapy
- Can be used to assist the surgery by ensuring cancer cells are removed in the operation and not in the bloodstream



- Specific and non-specific types
- Antibodies can target cancer, you can have a combination of mouse and human antibodies... one half of the antibody could be targeting one part and the other half of the head could be targeting another


Types of immunotherapy

- Monoclonal antibodies
- Programmed cell death pathway (PD-1)
- Chimeric antigen receptor (CAR) T-cells


Programmed cell death pathway (PD-1)

- Uses immune system to attack 'foreign' cancer cells
- Cancer hides behind inhibitors, this drug allows the immune system to see the drug
- It can make things worse if you have co-morbidities
- being used in lung cancer and melanoma


Chimeric antigen receptor (CAR) T-cells

- Artificial T-cell receptors, using retroviral vectors to give a specific cell killing function directed against cancer cells
- Very new
- In lymphomas and leukaemias, not solid cancers
- Side effects: you're taking lymphocytes out of circulation
- You put them back via T cell adoptive transfer


CAR T-Cells monitoring

- Disease response: CT scans, bone marrow biopsies, peripheral blood flow cytometry
- CAR T-Cell persistence: Immunohistochemistry of bone marrow biopsy, RT-PCR and flow cytometry of blood and bone marrow aspirate


Designer therapies

- Specific, based on molecular science
- You look at intracellular growth points
- EGFR inhibitor - in lung cancer need to have a specific mutaiton