CANCER INTRODUCTION Flashcards
which gender has most cancer overall
male
what is cancer
uncontrolled cell proliferation loss of natural apoptotic control decreased differntiation invasion ability to establish atypical environments loss of tissue organisation
How does cancer occur (3)
genomic instability
mutations
epigenetics
genes which can cause cancer
overexpression of oncogenes RAS or MYC,
faulty TSGs e.g. BRCA, p53
whats endogenous mutagenesis
chemical instability of DNA/ errors in replication
what can cause endogenous mutagenesis
oxygen free radicals produced in metabolism
lifetime exposure to oestrogen
other thing which can cause cancer- think more external
chemical carcinogens e.g. tabacco, environmental pollutants, alcohol
physical agenst such as UV or X-Rays
viruses and bactera e.g. HPV, H.pylori
what is epigenetics
means of altering the activity of genes by changing how compact or relaxed DNA is
effect of methylation
compacts DNA= reduced gene expression
effect of acetylation
relaxes- increases expression
ways proteins can cause cancer?
mutations
too much, too little, wrong place, less stable, more stable
what makes certain cells more prone to cancer?
as mutations occur in the S phase its more likley to occur in rapidly dividing cells e.g. epithelial lining of the gut
cells such as glial cells typically inhabit the g0 phase but can be stimulated to enter into division
what type of cells never divide?
myocardial
so unlikely to be cancer
4 classifications of cancer
Histopathology
grade
stage
metastasis
how to determine histopathology?
microscopic examination by biopsy
establishes origin of the disease and what type of cancer it is.
explain the grade of cancer? what makes it low or high grade? speed of growth?
low: well differentiated- look like normal cells, slow growth
high: less like normal cells, aggressive fast growth
what is staging? how do we present this?
how much of the disease is present TNM tumour size nodal envolvement metastases
TNM meaning and values
Tumour size 1-4, the bigger the side the higher the number
Nodal involvement 0 if local and 1 if <4 nodes and 2 if >4 nodes
Metastases either 0 or 1 if its gone into a different organ space- must be same cells as in primary tumour
3 ways of metastasis?
direct invasion- direct penentration through tissue
lymphatic spread
blood stream
generic presentation of cancer
lump
unexplained bleeding
weight loss
specific signs of cancer
chest pain
change in bowel habit
4 things that are used to confirm diagnosis
X-ray
biopsy
biomarkers
CT/PET
2 types of cancer surgery
palliative- to improve QOL
curative
what is curative surgery? would this be the only treatment?
primary tumour removal- no as high risk of relapse, probably chemotherapy
how would the tumours margins be classed as 0
in surgery the surgeon will take a sample from around the tumour, if no tissues found here the margins are 0
how do you qualify for palliative surgery? examples?
reasonable prognosis 3-6 months
e/g/ bowel obstruction
what can be used in place of surgery if the patient isnt fit enough?
radical radiotherapy- curative
what ways can radiotheapy be given in relation to surgery?
reduce size prioir to surgery
adjuvant: to consolivate surgery with chemo
palliative: to relieve symptoms of incurable disease
which type of radiotherapy is most common?
external beam radiotherapy
examples of external beam radiotherapy
Xray, electron, proton
what is stereotactic radiosurgery
cyber knife, avoids effects on surrounding tissue
what is total body irridiation?
fully ablate bone marrow before stem cell transplants
advantages of proton beam radiotherapy
reduces amount of RT administered to surrounding tissues, able to calculate it specifically to hit the tumour
useful for tissues which dont regenerate well
examples of internal radiotherapy
liquid radioiodine
selective internal radiation therapy (beads)
solid sources of RT
INTRACAVITY
interstitial- into tumour, stays forever and delivers radiation for 6-12 months
would an interstitial seed of RT make the person radioactive?
no, works locally
endogenous radiosensitiser?
oxygen: binds to breaks in DNA rendering them unfixable= cell death
exogenous radiosensitiser?
chemoradiotherapy e.g. cisplatin
gemcitabine
temozolomide, capecitabine, cetuximab
acute side effects of chemo?
rapidly dividing cells targetted: alopecia, N&V, indigestion, mucositis, taste disturbance, oesophagitis, diarrhoea, cystisis
late effects of chemo?
slowly dividing cells
fibrosis, breathlessness, lymphodema, bladder/ bowel incontinence, vaginal stemosis, sterility
when do acute side effects of RT present/ go away?
1-2 weeks into RT lasts for 3-4 weeks after
skin reactions in RT can be made worse by which risk factors?
older, smoking, alcohol, malnutrition, obesity
how to treat skin reactions? grades 1-4
grade1: moisturiser
2: m+ HYDROCORTISONE OR INSTILLAGEL
3: M, increase HC potency, dressings
4: consult
managing oral hygiene on radiotherapy?
pain pf mouth?
mucositis socium chloride/ bicarbonate, diflam stop smoking brush BD pain: mist paracetamol
how to manage RT associated N&V
5-HT3 receptor antagonist from 24 hours prior and 24 hours after treatment
ondansetrn or metoclopramide/ domperidone
low risk cancers for RT induced N&V? if prophylaxis used?
breast, head and neck, limb, brain, no prophylaxis used
treating cystitis from RT
antibiotics
treating diarrhoea from ABs
loperamide
what is SACT
systemic anti cancer chemotherapy
exampls of SACT
targetted agents
cytotoxic traditional chemo
immunotherapy
CAR-Ts
what do cytotoxic agents affect
all cells- depends on cell cycle stage in some
what must you do before giving targeted chemo?
establish expression of target, ensure to monitor for resistance
how does cytotoxic ?
interfered with cell cycle
kills cells and healthy cells
side effects of cytotoxic chemo
bone marrow suppression, N&V, alopecia, peripheral neyropathy
example of cytotoxic chemotherapy
capecitabine, flurouracil prodrug
capecitabine flurouracil MOA
antimetabolite, interfered with DNA replication enzymes
prevents thymidine production and halts DNA replication
which types of cytotoxic chemo is associated with peripheral neuropathy
platinums and taxanes
is alopecia and N&V seen with all cytotoxic drugs?
no, not all
N&V depends on emetogenicity of t he drug
how do targetted agents work
examples
disrupt ssignalling pathways which allows cancer cells to proliferate
TKIs
mAbs
what is gefitinib, what does it treat?
toxicities?
EGFR inhibitor, lung cancer, skin can give acneiform rash due to EGFR expression in the skin
GI disturbance
Cetuximab MOA
treats?
EGFR inhibitor
needs RAS wild type
treats RAS wild type colorectal cancer, cant use if mutated RAS
side effects of Cetiximab
acneform rash like TKI but no GI disturbances
hypersensitivity
what is a targeted cytotoxic agent?
combines two MOAs to increase efficacy and reduce toxicity
binds due to target and then releases cytotoxic agent
example of a targeted cytotoxic agent
trastuzumab HER2 receptor
trastuzumab MOA
HER-2 receptor specific
delivers a cytotoxic moiety as well
binds to HER2 cells only then releases= specific
what does immunotherapy utilise
T cells/ the immune cells
T cells normal role, how does cancer stop them?
they seek and destroy
cancer can express PD-1 which normally prevents autoimmune activity, but cancer uses it so T- cells cannot destroy them
how can we use immunotherapy to stop cancer deactivative T-cells using the PD-1 ligand?
PD-1 checkpoint inhibitor
toxicities of PD-1 checkpoint inhibitor?
autoimmune like conditions
colitis
pneumonitis
hepatitis
what is ATMP
advanced therapy medicinal products
example of ATMPs (advanced therapy medicinal products )
A gene therapy medicinal product
A somatic cell therapy medicinal product
A tissue engineered product
example of a ATMP
CAR-T
what does CAR-T treat? how are they made?
leukaemia T-cells taken from patient engineered to recognise cancer cells cultured to increase number returned into patient to destroy cancer
risk of using CAR-T cells
risk cytokine storm which can be life threatening
example of surgery RT and CT being used? give drug names
breast cancer
surgery to remove primary tumour if caught early
adjuvant chemo for micro metastases
radiotherapy for unclear margins at chest calls
1 year of trastuzumab or herceptin if HER+]5 YEARS OF ENDOCRINE THERAPY IF HORMONE RECEPTOR +VE E.G. TAMOXIFEN
