1st lecture Flashcards
normal cell prohibited from growing by ?
adjacent cells touching
tumor suppressors are?
susceptibility genes that survey the cell and prevents the cell from acquiring mutations
someone went to the doctor and they felt lump on their tongue and it wasnt there. last week. where did it come from?
it was there a long time and continued to get mutations because it takes a long time to accumulate mutations and getting the cancer
lead time bias
a flaw of many screening trials
catching cancers that are not going to kill people
lead time is
length of time btw detection of a disease and its clinical presentation and diagnosis
lead time bias is
the bias that occurs when 2 tests for disease are compared and one test diagnoses the disease earlier but no effect on outcome of the disease
telemerase
repeats of sequences where one sequence gets clipped off each time a cell divides
steps to turn. to a cancer
telemers are prolonged and keep divding forever not becoming scenescense by the hTERT gene
steps to turn. to a cancer
telemers are prolonged and keep divding forever not becoming scenescense by the hTERT gene
stops adhesion
inhibits apoptosis
invades
senescence cells
are flat cells that cannot replicate bc cannot put telomere at end of chromosome to replicate
carcinoma insitu
cancer fills the duct but cannot get out of duct
invasive cancer
when cancer learned how to make hole in basement membrane and go through
invasive phenotype is key to
metastasis and is what kills people
matrix metalloproteinases (MMPs)
are secreted by tumor and stromal cells
degrades extracellular matrix.
this degradation is key for metastatic and angiogenic processes
cell migration
- extension
- adhesion
- formaiton of actin filament
- traction
can you cure metastatic disease?
no it is a chronic disease so you live with your cancer
cancer stem cells stays if you give it ?
chemotherapy
cancer cells get into 100% serum and they live even though serum is
very toxic
the best place for a cancer to live is ?
where it was born because they live in a microenvironment where there is lots of support and nutrition
colonization
when cancer cell travels to another organ
angiogenesis
gives a cancer blood supply and is induced by hypoxia angiogenic factors FGF2 and VEGF. vascular cells grow into tumor
low vascular count =
live forever and makes difference in tumors
micrometastis
these cells travel to far places before you know you have cancer
makes you live less
patients with bone marrow micrometastases at diagnosis have
worse survival
frequency of cytokerative positive cells in bone marrow is ?
unaffected by chemotherapy
frequency of cytokerative positive cells in bone marrow is ?
unaffected by chemotherapy
adjuvant chemotherapy
used against micrometastases
cancer cells are not attacked by T cells because?
cancer cells have protein called PDL-1 that sends don’t eat me signal by blocking PD 1 (programmed death) receptor
10^12 (1kg)
death
10^9 (10g)
tumor causes first symptoms and is measurable and detectable
10 divisions you get
1000 cells
need 1 cubic cm tumor to?
see on xray
need 1 cubic cm (1g) tumor to? 30 cell division
see on xray and if anything less than 1 cubic cm then not considered a cancer
4 ways of getting chemotherapy
- induction treatment - no alternative therapy exists and is inoperable or metastic and to help pt live longer. use combo of drugs
- adjuvant chemo- cut out cancer and give treatment for less chance of cancer coming back. define response as complete, partial, stable or progression
- primary chemotherapy - to shrink tumor before surgery. and if you shrink it until looks gone, you must still do surgery to be 100% sure
- special use chemotherapy - highest concentration of drug against target tumor
4 ways of getting chemotherapy
- induction treatment - no alternative therapy exists and is inoperable or metastic
- adjuvant chemo- cut out cancer and give treatment for less chance of cancer coming. back
- primary chemotherapy (neoadjuvant) - to shrink tumor before surgery.
- special use chemotherapy - highest concentration of drug against target tumor
chemotherapy works best on ?
cycling cells
why give multiple drugs?
to hit different parts of the cancer cell metabolism bc made up of different clones of cancer
goldie - coldman hypothesis
give multiple drugs at once or cycle non-crossresistant regimens to interact with the many different clones of cancer cells. each time it divides it acquires more mutations.
combination chemotherapy
need combo of drugs for durable response
how would you know which drug to use?
if it worked in clinical trial
side effects of chemotherapy
chemo brain hair falls N/V cardiotoxicity \
side effects of chemotherapy
chemo brain hair falls N/V cardiotoxicity bone marrow suppression pulmonary toxicity chemical cystitis gonadal dysfunction - arrest of follicular maturation/destruction of ova and follicles
severe acneiform rash of CI-1040 MEK inhibitor in phase 1 trial means?
that the treatment is working
can measure treatment response by ?
biopsying the tumor
measuring lymphocytes in blood
antitumor agents associated with ?
Testicular germ cell depletion
ovarian dysfunction
alkylating agents caused?
ovarian failure
worse for testicular function too
key to licensing?
compliance monitoring
classification of chemotherapy cytotoxic agents
alkylating - full cell cycle and hits stem cells and affects dna
antimetabolites - work in s phase
mitotic inhibitors - m phase
anitibiotics - s phase and affects dna
chemotherapy works best on
cycling cells
what really hurts stem cells?
alkylating agent because works all throughout cycle and will modify dna and cause cell to die.
drug resistance
stem cells are drug resistant
pump out drugs
binding drug to protein that inactivates it
combination of chemotherapy accomplishes what 3 objectives?
maximal cell kill within range of tolerated toxicity
covers broad range of resistant cell lines
prevents or slows down new clone development
what drugs can you use to treat cancer?
only those tested in clinical trial that shrank tumor
the national research act of 1974 established?
the national comission -dentification of guidelines, ethical principles and regulation
aim of combination therapy?
increased efficacy
different mechanisms of action
different mechanisms of resistance
compatible side effects
micrometastatic
metastic tumor too small to be identified in scan
patients with bone marrow micrometastases at diagnosis have ?
worse survival
primary tumor metastasize to?
bone marrow
axillary lymph nodes
effects of vascular count and EGFR on survival are?
having low vascular count means you live longer
breast cancer progression
- genetic instability (mutation)
- loss of polarity
- loss of proliferative control by adjacent cells (adhesion molecule loss)
- exit from G0, entry to cell cycle- receptor, oncogene mutations
- Decreased ability to undergo apoptosis
- loss of scenscence, telomerase hTERT re-expression
- acquisition of invasive phenotype - key to metastasis
- acquisition of angiogenic phenotype, FGF2 VEG
name targets for chemotherapy
oncogenes
tumor suppressor genes
name cell cycle regulators
oncogenes
tumor supressor genes
invasive cancer
made hole through basement membrane and leads to primary cancer to metastasize
adverese effect assesment includes?
grade 0-4
was the event anticipiated
attribution or associatin to protocol therapy