Cancer Treatments Flashcards
Define oncogenes
Define tumour suppressor genes
How many oncogenes must be affected to cause cancer?
How many tumour suppressor genes must be affected to cause cancer?
- Proto-oncogenes regulate normal cell proliferation. When proto-oncogenes become either overexpressed or amplified (become oncogenes) it favours neoplasm formation
- Tumour suppressor genes normally supress neoplasm formation but in cancer these genes lose their function
- Number needed to be activated/lose function:
- Proto-oncogenes: 1
- Tumour supressor: 2
Describe the WHO performance status
Explain difference between radical and palliative treatment
- Radical treatment: given with intention of long term control or cure
- Palliative treatment: given to improve quality of life & relieve symptoms for pt, not focused on prolonging life
Explain the difference between local, regional and systemic treatment
- Local: treatment to localised region where cancer is
- Regional: treatment to area surrounding region where cancer is (e.g. may include lymph nodes)
- Systemic: affects whole body/treatment that reaches cells throughout the body by traveling through the bloodstream
Define:
- Neoadjuvant treatment
- Adjuvant treatment
- Maintenance therapy
- Neoadjuvant: treatment given before the definitive treatment
- Adjuvant: treatment given after the definitive treatment
- Maintenance therapy: treatment that is given to help prevent cancer from coming back after it has disappeared/remission following the initial therapy
State some options for cancer treatment
State some ways in which surgery is involved in the management of cancers
- Tissue biopsy (for diagnosis)
- Node biopsy (staging)
- Removal/resection of malignant tissue
- Repair, reconstruction & restoration of function following resection
- Palliative surgery (relief of obstructive symptoms, fracture reduction & fixation etc…)
Broadly summarise (in 1 sentence) how chemotherapy works to treat cancer
The chemo drugs target cells that grow and divide rapidly, as cancer cells do, and stop them from growing. They do this by interfering with cell division; by destroying the proteins involved in cell division or by specifically destroying the DNA of fast-growing cells in the body.
Remind yourself of the different classes of chemotherapy drugs and briefly describe how each works
(See CPT for more)
- Alkylating agents: reactive alkyl group with reacts to form covalent bonds with nuclei acids; then causes either cross-linking of 2 DNA strands preventing replication thus preventing further cell division.
- Antimetabolites: analogues of normal metabolites and they compete against natural metabolite; they can replace the natural metabolite and alter the normal cellular process
- Mitotic inhibitors: spindle poisons that can affect microtubules in two ways: either inhibit polymerisation (vinca alkaloids) so spindle fibres can’t form or stimulate polymerisation and prevent depolymerisation making microtubule so rigid it won’t work (taxanes); this prevents mitosis and arrests dividing cells in metaphase
-
Intercalating agents: work similar to alkylating agents but rather than directly forming cross strands in DNA molecule they bind between base pair molecules to prevent double DNA strand from dividing and hence preventing DNA replication
- Platinum compounds: (example/subdivision of intercalating agents) form interstrand and intrastrand adducts by binding specifically to guanine which cause cross linking of DNA and hence inhibit DNA replication and further cell division
- Topoisomerase inhibitors: block topoisomerase enzymes which are required for cell proliferation
- *Methotrexate (antimetabolite) works by antagonising the dihydrofolate reductase enzyme hence prevents regeneration of intermediates e.g. tetrahydrofolate. Tetrahydrofolate is essential for purine & thymidylate synthesis- both of which are essential for DNA synthesis. Hence, DNA synthesis is inhibited.*
- *5-FU (antimetabolite) is converted into 5-FdUMP (a fraudulent pyrimidine nucleotide) that can inhibit thymidylate synthase and hence inhibit DNA synthesis*
State some examples of drugs in each of the chemotherapy drug classes
- Alkylating agent: cyclophosphamide
- Platinum compounds: cis-platin
- Antimetabolites: methotrexate, 5-Fluorouracil
- Mitotic inhibitors: vinca alkaloids (e.g. vincristine) & taxanes (e.g. paclitaxel)
- Topoisomerase inhibitors: etoposide
Describe some mechanisms by which cancer cells can become resistant to chemotherapy
- Altered cell transport mechanisms to prevent drug concentration in cancer cells by either reducing uptake or increasing efflux
- Altered drug metabolism to increase clearance or reduce drug activation
- Altered biochemical pathways to avoid specific pathway blocks
- Impaired mechanisms of apoptosis
State some factors that influence the dose of chemotherapy we would give to a pt
- BMI and/or SA
- Drug handling ability (e.g. renal func, liver func)
- General wellbeing (performance status)
State some routes of administration for chemotherapy- highlight which is most common
- IV (most common) **Can be given via indwelling venous catheters
- PO
- SC
- Intralesional
- Intrathecal
- Topical
- IM
Explain the difference between a portacath, Hickmann & Picc line
- Hickmann: insert under radiological control using LA. Cather is tunnels under skin and then into the subclavian vein and ends in the SVC
- PICC line: simpler to insert than Hickmann but less robust. Insert in antecubital vein and ends in the SVC
- Portacath: small chamber or reservoir that sits under the skin at the end of your central line. The other end of the line sits in the SVC.
State some acute side effects of chemotherapy
State some potential long term side effects of chemotherapy
- Development of other cancers (particularly leukaemia)
- Damage to heart muscle (cardiomyopathy)
- Damage to lungs (e.g. bleomycin → pulmonary fibrosis)
- Infertility
- Chemo-brain (some people notice changes in their memory, concentration and the way they think)
How does radiotherapy work to treat cancer?
Radiotherapy uses high energy rays, such as x-rays, to damage DNA (either directly or indirectly due to toxic free radicals); this causes apoptosis if cell is unable to repair the DNA.
Radiotherapy can be given pre-operative or post-operatively; state some advantages/reasons for each
State and describe some different methods of delivering radiotherapy
-
External beam
- Conformal: radiation beam shaped to shape of the cancer to minimise damage to surrounding tissue
- IMRT (intensity modulated radiotherapy): each radiotherapy beam is divided into many small beamlets that can vary the intensity of radiation allowing different doses of radiation to be given across the tumour.
- IGRT (image guided radiotherapy): uses scans/imaging whilst pt on the radiotherapy couch to ensure they are in correct position
- Stereotactic radiotherapy: radiotherapy from many different angles around the body. The beams meet at the tumour.
- Proton beam therapy: high energy or low energy proton beams to treat cancer. Most people’s radiotherapy uses x-rays
- Superficial radiotherapy to the skin:
-
Internal beam
- Radioactive liquid: radioactive substance taken as a drink, capsule or injection. Radioactive substance travels through body but mostly collects in area where cancer cells are
- Brachytherapy: put radioactive material into body (into or very close to cancer or even where cancer was removed)
In radiotherapy terms, what is:
- A fraction
- Gray
- Fractions= number of treatments of a given dose
- Gray= unit of radiation dose
State some acute side effects of radiotherapy
- Many pts experience fatigue
- Other affects dependent on area treated:
- Erythema (leading to desquamation if severe)
- Diarrhoea
- Nausea & vomiting
- Dysuria
- Increased frequency urination
- Hair loss
- Mucositis
State some long term side effects of radiotherapy
- Skin: pigmentation, fibrosis, telangiectasia
- Bowel: stricture, adhesions, fistulas
- Bladder: fibrosis causing frequency, fistulae
- Bone: necrosis, impaired growth in children
- CNS: myelitis causing paraplegia
- Lung: fibrosis
- Heart: cardiomyopathy
- Eyes: cataracts, loss of vision
- Gonads: infertility, early menopause
How do immunotherapies work in the treatment of cancer?
State some examples of different types of immunotherapy and how they work
- Immunotherapies target the immune response provoked by tumour antigens
- Put simply “Tumour antigens can interact with cells in immune system to decrease the immune systems response and allow tumour to grow”
- There are different types of immunotherapy; but when people talk about immunotherapy they are most commonly referring to checkpoint inhibitors
- Checkpoint inhibitors: checkpoints keep the immune response from being too strong; inhibiting these checkpoints allows the immune cells to respond more strongly to the cancer
- T-cell transfer therapy: boosts the natural ability of the pt’s T cells to fight cancer; take immune cells from tumour and modify those that are most active against cancer so that they can better attack cancer then put back into body
- Monoclonal antibodies: antibodies that specifically target the cancer cells are made in the lab; these mark the cancer cells so they are better recognised and destroyed by immune system
- Treatment vaccines: boost your immune system’s response to cancer cells
Briefly explain how checkpoint inhibitors, example of immunotherapy, work
- Checkpoints keep the immune response from being too strong; inhibiting these checkpoints allows the immune cells to respond more strongly to the cancer
- Tumour antigens bind to protein 4 (CTLA-4) and programmed death (PD)-1 binding sites on cytotoxic T lymphocytes (CD8 cells)
- This results in downregulation of immune response to tumour allowing tumour growth
- Therefore, drugs that block these receptors prevent downregulation of immune response/enhance immune response to cancer cells
CTLA4 inhibitor
- Imipilumumab
- Used in Melanoma
PD-1/PD-L1 inhibitors
- Nivolumab
- Pembrolizumab
- Used in melanoma, lung, renal cancers
State some examples of when immunotherapy is used in cancer treatment
- Melanoma
- Lung cancer
- Renal cancer
- Bladder cancer
State some potential side effects of immunotherapy
Immunotherapies can have lots of side effects affecting lots of different systems. Symptoms related to inflammation in the organ (e.g. colitis, hepatitis, nephritis, pneumonitis, endocrinopathies such as hypopituitarism)
- GI: diarrhoea, abdo pain, blood and/or mucus in stool, bowel perforation, ileus
- Skin: pruritis, rash (SJS or TEN), dry skin
- Neurological: weakness, parasthesia, sensory alterations, myasthenia gravis, Guillian Barre syndrome
- Hepatitis
- Endocrine: hypophysitis, hypopituitarism, hypothyroidism, adrenal insufficiency
- Eyes: conjunctivitis, blepharitis, episcleritis, uveitis, scleritis
- CVS: myocarditis, temporal arteritis
- MSK/rheum: arthritis, PMR
What is targeted therapy?
- Targeted cancer drugs work by ‘targeting’ those differences that help a cancer cell to survive and grow
- There are many different types of targeted drugs. They are grouped together depending on how they work (but note there can be overlap). Groups include monoclonal antibodies, cancer growth blockers, drugs that block cancer blood vessel growth and PARP inhibitors.
State some examples of when targeted therapies are used in cancer treatment
- Breast cancer (Hercpetin)
- Leukaemia (rituximab)
- Lung cancer
State some side effects of targeted treatments used in the treatment of cancer
- Diarrhoea
- Fatigue
- Mouth sores
- Dry skin
- Skin rashes
- Loss of appetite
- Oedema
… lots of non-specific symptoms similar to those associated with chemotherapy
Discuss the challenges of survivorship
- Uncertainty about future
- Health anxiety
- Changes to relationships/relationship struggles
- Long term physical effects from treatment e.g. fertility, altered appearance, fatigue
- Long term emotional & cognitive effects e.g. anxiety, depression, chemo-brain
- Financial and work problems
In radiotherapy terms, what is:
- A fraction
- Gray
- Fractions= number of treatments of a given dose
- Gray= unit of radiation dose
What are telomeres?
What is the role of telomerases?
What can happen to telomerases in cancer cells?
- A telomere is the end of a chromosome. Telomeres are made of repetitive sequences of non-coding DNA that protect the chromosome from damage. Each time a cell divides, the telomeres become shorter. Eventually, the telomeres become so short that the cell can no longer divide.
- Telomerase is the enzyme responsible for maintenance of the length of telomeres/can extend the telomeres
- Cancer cells may reactivate telomerases allowing them maintain length of telomere and to continually divide
What is immunophenotyping?
State some different types/methods and when each may be used
State some examples of situations in which immunophenotyping is used
- Use of antibodies to detect antigens on cells (think about word ‘immuno=antibodies’, ‘phenotyping=antigen expression’)
- Types:
- Flow cytometry: fluid e.g. blood
- Immunohistochemistry: used if have a tissue sample
- Immunocytochemistry: used if have liquid other than blood e.g. FNA from lymph node
- Uses:
- Identify lymphocyte subset (e.g. B or T cell in CLL)
- Distinguishing CLL from reactive lymphocytosis (can tell you if lymphocytes are monoclonal or polyclonal)
- AML diagnosis (& helps guide treatment)
- Distinguishing MGUS & myeloma (% of blast cells)
What is cytogenetics?
State some different types/methods of cytogenetics
State some uses of cytogenetics
- Studies the structure of DNA within the cell nucleus
- Different types/methods:
- FISH: involves labelling probes with fluorescent dyes and using this to look for ‘larger changes’ e.g. translocations, deletions, trisomy’s etc…
- PCR: smaller mutations (e.g. JAK2 mutations)
- Uses:
- Prognosis in cancers e.g. AML
- Risk factors & diagnosis e.g. JAK2 in myeloproliferative disease
Bone marrow biopsies are sent for immunophenotyping (to check for clonality) and cytogenetics (high risk genetics)
State some side effects of following chemotherapy drugs:
- Asparagine
- Cisplatin
- Doxorubicin
- Bleomycin
- Vincristine
- Vinblastine
- Cyclophosphamide
- Methotrexate
- Asparagine: central neurotoxicity: excessive sleepiness, depression, hallucinations, agitation, disorientation or seizure
- Cisplatin: ototoxcity, peripheral neuropathy, hypomagnesaemia
- Doxorubicin: cardiomyopathy
- Bleomycin: pulmonary fibrosis
- Vincristine & vinblastine: peripheral neuropathy
- Cyclophosphamide: haemorrhagic cystitis
- Methotrexate: myelosuppression, mucositis, liver fibrosis, lung fibrosis
State the mechanism of action of the following chemotherapy drugs:
- Methotrexate
- 5-FU
*
- Methotrexate: Inhibits dihydrofolate reductase and thymidylate synthesis
- 5-FU: Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase)
State 2 examples of cytotoxic abx
- Bleomycin
- Doxorubacin
