Chemotherapy Flashcards
What characteristics do cancer cells exhibit not seen in normal cells?
- uncontrolled proliferation
- Invasiveness
- Metastases
Main causes of cancer
- Mutations in DNA - production of altered cells which have changes in proliferating mechanisms
- Changes in DNA caused by covalent modifcation
- spontaneous or genetic predisposition
- ionising radiation or UV radiation
- chemical carcinogens
What are the 3 types of treatment of cancer
- sugrical excision
- radiotherapy
- chemotherapy
What are the 4 traditional agents of chemotherapy?
- alkylating agents
- antimetabolites
- cytotoxic antibiotics
- plant derivatives
What is the mechanism of action of alkylating agents?
forming covalent bonds eith suitable nucelophilic substances un the cell causing intrastand linking and cross-liking of DNA. Damage to the DNA of the cells triggers cell death by apoptosis
What are the 6 major groups of alkylating agents and give an example of each
- Nitrogen mustards - e.g. cyclophosphhamide
- Ethyleimines - e.g. thiotepa
- Alkylsuphonate - e.g. busulphan
- Hydrazines and Triazines - e.g. Temozolomide
- Nitrosoureas - e.g. lomustine, carmustine
- Platinum based compounds - e.g. cisplatin
What are the 3 major groups of antimetabolites and give an example of each?
- Antifolates - e.g. methotrexate
- Antipyrumudines - e.g. 5-UF, gemcitabine
- Antipurines - e.g. mercaptopurine, thioguiane
What is the mechanism of action of antifolates?
Folate analogue so inhibits normal metabolic pathways in cancer cells
What is the mechanism of action of antipyrimidines?
5-UF = inhibits thymidylate synthesis (metabolic pathways)
inhibits DNA polymerase
What is the mechanism of action of antipurines?
Fradulent nucleotide so prevents DNA replication
Give the 4 main cytotoxic antibiotics and what is their main mechanism of action?
direct action on DNA
- Anthrayclines - Doxorubicin (inhibits DNA and RNA synthesis)
- Dactinomycin (interfers with the movement of RNA polyermase)
- Bleomycins (chain fragmentation and release of free bases)
- Mitomycin (cross-links DNA)
What is the mechanism of action of chemotherapy plant derivatives?
spindle poisons - affect microtubule function and prevent miotic spindke formation or topoisomerase I/II inhibitors
What are the 4 main chemotherapy plany derivatives
- Vinca alkaliids - vincaristinen, vinblastine (spindle)
- Taxanes - paclitaxel, docetaxel (spindle)
- Camptothecins - irinotecan (top I)
- etoposide (top II)
Give three examples of monoclonal antibodies as anticancer drugs with novel targets
- Rituximab - targets B cell surface protein and is used for B cell lymphomas
- Trastuzumab (Herceptin) - targets epidermal growth factor receptor and is used for breast cancer
- Imatinib (gleevac) - inhibits bcr-abl gene signalling pathways and is used for CML
Other examples of novel targeted agents in treating cancer
- hromones
- protein kinase inhibitors
- miscellaneous agents
What are the major drawbacks of the current cancer chemotherapy treatment
- target cell proliferation not more lethal properties
- non-specific
- resistance is developing
- total elimination of cancer cells is not possible with theraputic doses
- bone marrow, hair, GI mucosa and skin are mainly affected
- Side effects occur 7-14 days post treatment and can be accumulative
- reduced patient compliance due to side effects
Describe Tumour lysis syndrome
- acute side-effect and metabolic emergency
- occurs due to rapid cell lysis and large amounts of metabolites in the blood
- characterised by hyperuricaemia, hyperphosphatemia, hyperkalaemia and hypocalcaemia
- Can lead to acute renal failure, cardiac arrest and death
What is myelosuppression?
reduced production of cells which provide immunity, oxygen transport and clotting
*common with many chemotherapy agents
Side effect that affects the bone marrow and short lived cells
GI side effects of chemotherapy
- Nausea and vomitting
- Loss of appetite
- Constipation
- Diarrhoea
- Ulcerationm dry mouth, pain, taste alterations
Other specific side effects assoicated with chemotherapy
- fatigue
- body image
- peripheral neuropathy
- altered renal function
- delayed effects
Give an example of a highly, moderate and mild emetogenic cancer drug and how would this be treated?
- High = cisplatin
- Moderate = doxorubicin
- Mild = etoposide
lorazepam (pre treatment), steroids (dexamethazome), anti-emetics (ondersartan, metoclopramide)
What does personalised medicine take into account?
- genomic/genetic testing
- proetomic profiling
- metabolomic analysis
What are the 4 Ps of personalised medicine?
Predicitive
Personalised
Preventative
Participatory
What did doctors traditionally use for prescribing treatment?
- family history
- socio-economic circumstances
- environmental factors
Aims of the NHS with regards to personalised medicine
- prediction of disease and targted prevention
- early identification
- precise diagnosis
- targeted interventions
- imrpoves outcomes
- reduce costs
Personalised medicine drugs for NSCLC
- AKL rearrangements are mutally exclsuive with EGFR and KRAS mutations
- activating mutation = locks on activity of mutant action
- EGFR = erlontinib
- KRAS = no drug
- ALK rearrangement = crizontinib
Personalised medicine drugs for colorectal cancer
- cetuximab - anti-EGFR monoclonal antibody therapy
- RAS mutation = lack of response to thearpy
Personalised medicine drugs for Melanoma
BRAF -= vermurafenib; inhibitor of mutated B-Raf
NRAS mutations: MEK inhibitors/ KIT (c-kit) mutations; imatinib
Personalised medicine drugs for Brain tumours (high grade glioblastomas)
Temozolomide: alkylatin agent (+ radiation)
if there is MGMT promoter gene methylation (DNA repair enzyme)
What is FISH analysis used for?
- Ewing’s sarcomas
- alveolar rhabdomucosarcomas
- leiomycosarcomas
- fibromyxoid sarcomas
