Week 12 - CNS Tumours and Holistic Cancer Care Flashcards
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
