from lecture - genes, mechanisms Flashcards
difference between passenger mutations and driver mutations
Passenger mutations occurs within tumours but cause no change in the phenotype present – don’t change properties of cells
Driver mutations are mutations the cell acquires in addition to the initial mutation that contributes to the development of cancer. Knowing these mutations allows targeted therapies
what are the 4 different methods of spread of metastases
trans-coelomic spread
lymphatic spread
hematogenous spread
perineurial spread
what is transcolomic spread
occurs when a malignant neoplasm penetrates into a natural open field lacking physical barriers eg peritoneal and pleural and pericardial and joint spaces.
e.g. ovarian cancer to peritoneal cavity
what is lymphatic spread
through lymphatic vessels located at tumour margins and follow drainage e.g. cervix to internal iliac
hematogenous spread
cells of primary tumour penetrate into blood tumour - venous or arterial
perineural spread
along a nerve
lung cancer spread too
adrenal glands, brain and bone
breast spread to
bone, liver lung and brain
colon spread to
liver
pancreatic spread to
liver and lugns
ovarian spread to
pleural cavity and lungs
prostate
bone
phases of metastatic cascade
invasion of Extracellular matrix - loosening up tumour cell interactions( normal epithelia glued by e-acdherins) , degradation of ECM , attachment tp ECM commonest and migration and invasion
vascular dissemination
In their normal, unmutated state, onocgenes are called
proto-oncognees
Mutagens
are agents that cause changes in DNA and can be chemical like tobacco tars or physical like x-rays
carcinogen
are mutagens and induce cancer through mutation of critical growth controlling genes in susceptible cells. Most carcinogens are mutagens but not all ,mutagens are carcinogens eg a protooncogene – once mutated may become an active oncogene driving cancerous growth
SRC
colon cancer
ABL
CML
erbB
breast cancer
fms
AML
raf and h-ras
bladder cancer
what are proto oncogenes
normal gene often involved in normal growth control, may become oncogenes through mutation affecting a specific activity conferring a selective advantage
ras oncogenen associated with
pancreas
what type of mutation affects p53
• Missense mutations can inhibit p53 from binding to its target genes,
cancer can be familial, hereditary ( germline) or sporadic ( somatic ) wha tis most common
Somatic mutations – initially arise in one cell
indications of a gremlin mutation
Bilateral tumours or multifocal multi-germline
Young age
Certain histology eg triple negative breast cancer
Examination findings eg macrocephaly skin and abnormalities
Family history
what does the Manchester score look for
The Manchester Scoring System (MSS) allows the calculation of the probability for the presence of mutations in the BRCA1 and BRCA2 genes in families suspected of having hereditary breast and ovarian cancer
what is Lynch syndrome
lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is a type of inherited cancer syndrome associated with a genetic predisposition to different cancer types
what is the difference between EBV causing bruits lymphoma, B cell lymphomas, and nasopharyngeal cancers
in the burkitt lymphomas 8:14 translocation is positive
B cell and naso its negative
IS H.PYLORI A carcinogen
yes only bacteria
what is flow cytometry
Flow Cytometry is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles
antigen specific T cells can control cancer this enables immunotherapeutics such as adoptive T cell transfer and checkpoint blockade eg
CTLA-4 and PD-1
Pharmacogenetics
study of genetically determined variations that are revealed solely by the effects of drugs
Pharmacogenomics
describes interaction between drugs and the whole genome
allopurinol can cause
stevnes johnson syndrome
what HIV drug that is a reverse transcriptase inhibitor can have adverse side effects
Abacavir
pharmacokinetics
- This the study of what body does to the drug
4 commonest of pharmacokinetics
- Absorption – substance entering blood circulation
- Distribution – dissemination of substances through fluids and tissues of the body
- metabolism is recognition by the organism that a foreign substance is present and the irreversible transformation of parents compounds into daughter metabolites – genetic variation most commonly affects this
- excretion – removal of substance from the body
types of metabolisers
ultra rapid – higher than usual
extensive – normal enzyme activity
intermediate – lower
poor metabolisers
poor may not help and ultra may leads to esymtposm of overdose
what can cause repiroatry depression in children when
codeine
Pharmacodynamics
drug to body
treatment for CML
imatinib
Imatinib blocks ATP binding centre of Bcr-abl thus inhibiting its phosphorylation activity
Colorectal cancer
EGFR overexpressed in most
Wild type KRAS is required for response to anti-EGFR targeted antibodies
KRAS mutant – no response to panitumumab
KRAS wild type more response to this
in Her 2 postive ( human epidermal growth factor receptor 2) breast cancer what can we use to treat it
Trastuzumab is a HER2 targeting monoclonal antibody approved for treatment of HER2
PARp inhibitors are a treatment for some women who have a fault in one the BRCA genes and one of the following types of cacner, - ovarian, fallopian tube and peritoneal cancer
Terminal illness or end stage disease
is a disease that cannot be cured or adequately treated and is reasonably expected to result in death of the patient
coping
to struggle or deal especially on fairly even terms or with some degree of success
Deal with responsibilities, problems or difficulties especially successfully or in a calm or adequate manner
Kupler ross stages
Shock and denial Anger Bargaining Depression Acceptance
