Week 12 - CNS Tumours and Holistic Cancer Care Flashcards
(12 cards)
How are primary tumours graded
Primary CNS tumours include malignant, benign and borderline tumours
Graded on how likely they are to spread
Grade 1-2 = low grade
Grade 3-4 = high grade / malignant
What are the risk factors for brain tumours
- High dose ionising radiation
- this is the only unequivocal risk factor that was identified for glial and meningeal neoplasms
- Genetics
- Ethnicity (greater risk in white people)
- Gender (females)
- menopausal hormone therapy = increased risk - Viral infections
Clinical presentation / symptoms of brain tumours
- Headache
- Seizure
- Focal deficiency sympotms
- loss of vision, balance problems, numbness etc. - Disorientation
- Changes in personality or cognitive impairment
CAUSE:
- obstruction of CSF flow
What are the primary treatments for brain tumours
- Radiotherapy / Chemotherapy
- radiotherapy is done via using photons (x-rays)
- mainstream treatment of tumours not cured by surgery
- Pharmacotherapy
- i.e. Dexamethasone, Temozolomide and MGMT methylation
Some Pharamoctherapies
Not MAIN ones to know
Dexamethasone:
- Given with PPI
- Manage oedema + associated clinical symptoms
Vinblastine:
- 1st line ot for relapsed low grade glioma
- Max. 10mg
- SE: bone/jaw pain, peripheral neuropathy
Temozolomide (TMZ) Use
Pharmacotherapy
Treatment for Gliobastoma and GBMs
- types of primary brain tumours
- Gliobastoma - a cancer derived from gilal cells (brains support cells)
- TMZ is a triazene
- dose can increase or decrease on each cycle of tretament depending on patients symptoms
- SE: N&V, consitaption
- generally well tolerated
Temozolomide MoA
Pharmacotherapy
- Undergoes rapid chemical conversion at physiological pH to its active form MTIC
- MTIC is cytotoxic (kills cells)
- due to akylation at O6 and N7 position on DNA bases
- cytotoxic lesions repair the methyl adduct
MoA:
- TMZ is a prodrug that is converted into its active form MTIC
- MTIC decomposes to form an ion that akylates DNA at O6 position = methyl DNA is formed
- Akylation of DNA interferes with its replication
- during replication errors may occur which triggers the DNA repair mechanism
- DNA repair enzyme (MGMT) corrects the damage by removing methyl (added by TMZ)
- TMZ inihbits MGMT action = prevents repair of DNA = accumulation of DNA damage
- persistent DNA damage activates apoptosis = cell death (of cancer cells)
NOTE:
- TMZ has a low LogP and high PSA (both out of usual ranges)
- diffuses into CNS poorly
- once converted can NOT diffuse out as the active form has even WORSE properties
How can resistance to TMZ treatment occur
- Overexpression of MGMT = methyl is removed form position O6 = no more DNA damage = no apoptosis
- Enhanced DNA repair capacity within cancer cells
- Reduced rug exposure of TMZ
- Upregulation of AETs = TMZ is removed from brain cells back into blood
- Changes in TMZ pharmacokinetics
- Genetic mutations = genes involved in DNA repair are affected
What is the role of TMZ in its effectiveness linking in the Hallmarks of Cancer
TMZ targets key cancer hallmarks
TAREGTS:
1. Uncontrolled cellular proliferation / growth
- interferes with DNA replication
- Angiogenesis
- inhibits formation of new blood vessels = cells recieve no nutrients = no growth
- Apoptosis (cell death)
- induces DNA damage (methylation at position O6) = activates apoptosis
- Invasion and Metastasis
- inhibits cell migration + invasion = prevents spread of tumour
- Sustained proliferative signalling
- targets DNA replication + cell division
- is cytotoxic ~ disrupts this signalling + inhibit growth signalling
What is the role of MGMT in its effectiveness linking in the Hallmarks of Cancer
MGMT - methylated GBMs | Pharmacotherapy
- MGMT (gene) that encodes an enzyme involved in DNA repair
- when methylation occurs = inadequate DNA repair due to alkylating chemo
MoA:
- MGMT remove alkyl adducts from O6 position on guanine at DNA level = antagonsing effects of alkyl agents
What is Holistic Needs Assessment (HNA)
- Assessment / discussion where patient talks through needs + concerns with a HCP
- concerns can be related to any area of their life not just physcial symptoms of cancer or SE of treatment
Concerns can be:
- physical
- emotional
- practical
- financial
- spiritual
Outline the name and mechanism of action of at least SIX susceptibility genes associated with epileptic symptoms in patients with neurological tumours
- BRCA1 and BRCA2
- BRCA = Breast Cancer
- Mutuation / dysregulation in ion channel genes due to SCN1A or SCN2A
- Mutation in ion channel function due to NF1, NF2
- NF = neurofibromatosis
- Variation in neurodevelopmental genes e.g. ARX, RELN
