CANCER- the biological basis of cancer therapy Flashcards
what are the 6 most common cancers worldwide? in terms of mortality
lung breast bowel prostate stomach
what are the main anti-cancer treatments?
surgery
radiotherapy
chemotherapy
immunotherapy
what types of mutations can cause cancer?
Chromosome translocation
Gene amplification (copy number variation)
Point mutations within promoter or enhancer regions of genes
Deletions or insertions
Epigenetic alterations to gene expression
Can be inherited
what is cytotoxic chemotherapy
affects rapidly dividing cells- non “targeted”
given by IV
works systemically
ADJUVANT given post operatively- “mops” up any remaining cancerous cells
NEOADJUVANT given pre operatively
can be given on its own or in combination
what are alkylating agents
Cross-link (intra, inter, DNA-protein) DNA strands and prevents DNA from uncoiling at replication Trigger apoptosis (via checkpoint pathway)
eg. Chlorambucil, cyclophosphamide, dacarbazine, temozolomide.
what are pseudo-alkylating agents?
Add platinum to guanine residues in DNA
Same mechanism of cell death as akylating agents
eg. carboplatin, cisplatin, oxaliplatin
what are the side effects of alkylating and pseudo-alkylating agents?
cause hair loss (not carboplatin), nephrotoxicity, neurotoxicity, ototoxicity (platinums), nausea, vomiting, diarrhoea, immunosuppression, tiredness
what are anti-metabolites?
Block DNA replication (DNA-DNA) and transcription
what are the side effects of anti- metabolites?
Hair loss (alopecia) – not 5FU or capecitabine
Bone marrow suppression causing anaemia, neutropenia and thrombocytopenia
Increased risk of neutropenic sepsis (and death) or bleeding
Nausea and vomiting (dehydration)
Mucositis and diarrhoea
Palmar-plantar erythrodysesthesia (PPE)
Fatigue
what are anthracyclines?
Inhibit transcription and replication by intercalating (i.e. inserting between) nucleotides within the DNA/RNA strand.
Also block DNA repair - mutagenic
They create DNA and cell membrane damaging free oxygen radicals
Examples: doxorubicin, epirubicin
what are the side effects of anthracyclines?
Cardiac toxicity (arrythmias, heart failure) – probably due to damage induced by free radicals Alopecia Neutropenia Nausea and Vomiting Fatigue Skin changes Red urine (doxorubicin “the red devil”)
what are vinca alkaloids and taxanes?
Work by inhibiting assembly (vinca alkaloids) or disassembly (taxanes) of mitotic microtubules causing dividing cells to undergo mitotic arrest
what are the side effects of vinca alkaloids and taxanes?
Nerve damage: peripheral neuropathy, autonomic neuropathy
Hair loss
Nausea
Vomiting
Bone marrow suppression (neutropenia, anaemia etc)
Arthralgia
Allergy
what are Topoisomerase inhibitors?
Topoisomerases are required to prevent DNA torsional strain during DNA replication and transcription
They induce temporary single strand (topo1) or double strand (topo2) breaks in the phosphodiester backbone of DNA
They protect the free ends of DNA from aberrant recombination events
what are the side effects of Topoisomerase inhibitors?
(irinotecan): Acute cholinergic type syndrome – diarrhoea, abdominal cramps and diaphoresis (sweating). Therefore given with atropine Hair loss Nausea, vomiting Fatigue Bone marrow suppression
