Chemotherapy Flashcards
What are the 4 types of chemotherapy
Neo-adjuvant - given before surgery to reduce tumour size
Adjuvant - Chemotherapy given to destroy left-over (microscopic) cells that may be present after the known tumor is removed by surgery.
Palliative
Immunotherapy
Why is chemotherapy given in 3 week cycles
To allow bone marrow cells to recover - they are also targeted as they are rapidly dividing
Antimetabolites - describe their action , give an example
Interfere with metabolic pathways in DNA synthesis
Folate antagonist - prevent synthesis of nucleotides
False substrates mechanism of action
Pyrimidine analogues
Inhibits thymidylate synthase
Incorporated into DNA leading to damage of DNA = cell dies
Alkylating agents - mechanism of action
More side effects
Causing cross linking of DNA via alkylation = DNA cannot unwind = defective DNA replication
Platinum chemotherapy - mechanism of action; main side effect
Inhibition of DNA synthesis by cross-linking guanine residues (prevent helix from unwinding )
Nausea with use is very common
Anthracycline antibiotics - mechanism of action; adverse effect
intercalation (slotting between) DNA strands –> inhibition of topoisomerase (involved in uncoiling of DNA) + free radical generation –> inhibition of DNA synthesis
Cardio toxicity is a side effect
Topoisomerase II inhibitors
Inhibition of topoisomerase II presents ligation of DNA leading to breaks in DNA
Microtubule inhibitors
Vinca alkaloids block the formation of mitotic spindle - required for mitosis
Taxanes stabilise spindle fibres - this prevents the migration of chromosomes during anaphase
Side effects of chemotherapy
Inhibit growth of gut epithelia and hair loss
Myelosuppression can lead to anaemia and low neutrophil counts (neutropenic sepsis due to decreased resistance to infection)
Infertility
Cardio toxicity - damage to heart muscle resulting in impaired heart activity (SoB, chest pain, peripheral oedema, palpitations and dizziness)
Treating side effects if chemotherapy
Colony stimulating factors to increase WBC count
Prevent infections with antibiotics and anti fungal
Describe the principle of targeted anticancer therapy.
Exploits faulty genes/signalling pathways/tumour growth/angiogenesis
Hormonal targets
Molecular testing to determine receptor expression
Describe the relevance of human epidermal growth factor receptor-2 as a target in anti-cancer treatment.
Naturally present in low levels but over expressed in some cancers, breast cancer most commonly
Due to oncogene activation
Affects gene transcription and cell cycle
Describe the role of tyrosine kinase inhibitors in anticancer treatment. identify the two cancer they usually used for
Tyrosine kinase leads to uncontrolled cell proliferation
Imatinib inhibits TK activity
Selective inhibitor very effective for Chronic Myeloid Leukaemia
Also used for gastro-intestinal stroma tumours
Describe the role of proteasome inhibitors in anticancer treatment.
Proteosomes: cellular structures which degrade proteins
Some proteins kill cancer cells: pro-apoptotic factors
Inhibition of intracellular proteasomes alters the regulation of intracellular proteins
eg bortezomib used in multiple myeloma
Describe the role of anti-VEGF based drugs in anticancer treatment.
Vascular Endothelial Growth Factor
VEGF secreted to promote angiogenesis
Angiogenesis: blood vessel growth to support metastasis
Bevacizumab: monoclonal antibody
Advanced colonic and breast cancer
Sunitinib: inhibits VEGF-associated receptor tyrosine kinase
Advanced renal carcinoma
Symptoms of ovarian cancer
Abdominal pain Persistent indigestion/nausea Bloating Pain during sex Altered bowel habits Back pain Vaginal bleeding Tired all of the time Unintentional weight loss
Tamoxifen - describe its mechanism of action
Blocks oestrogen as a selective estogen-receptor modulator (SERM)
Prevents breast cancer /reduces growth of breast cancer (must be ER +)
Also prevents bone loss
Aromatase inhibitors
Androgens converted to oestrogens via aromatase in post-menopausal women
Oestrogens promote tumour growth in ER+ breast cancers
what is the philadelphia chromosome? which cancer is it associated with?
An abnormality of chromosome 22 in which part of chromosome 9 is transferred to it; associated with Chronic Myeloid Leukaemia
produces bcr-abl protein which promotes tyrosine kinase activity
Describe the epidermal growth factor (EGF receptor) kinase
they are a type of tyrosine kinase receptors
epidermal growth proteins are needed for cell signaling pathways that control cell division and survival
PARP inhibitors - mechanism of action; which cancers are treated with them?
PARP is a DNA-repairing enzyme (single-strand break)
BRCA genes important in DNA repairs - if mutation occurs here = PARP inhibition = inability of cancer cells to repair double strand breaks=cell death
used for breast, prostate and ovarian cancer
