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
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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
Radiotherapy can be given pre-operative or post-operatively; state some advantages/reasons for each
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
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 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)
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
