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Flashcards in cancer biology Deck (127)
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what is the single most important feature of a cancer cell, distinguishing it from a normal cell?

cancer cells have genetic and epigenetic instabilities


what is meant by long latency period?

this means the time for the cancer to be clinically detectable is quite long - by the time it can be detected patients may die of other reasons


how do know that DNA repair mechanisms protect us from cancer?

xerosteroma pigmentosum, which cause be an autosomal recessive mutation to the nucleotide excision repair enzyme - patients cannot repair dimerised pyrimidine formed due to exposure to UV light - and have more freckles and a much higher chance of skin cancer


apart from DNA repair mechanisms, what else protects us from developing cancer?

immunity protects us, and this is evident by the fact that immunosupressed renal patients have a much higher incidence of cancer than the general population


why is cancer very difficult to cure?

because it is genetically heterogeneous (conferring different sensitivity to treatment)
very similar to normal body cell- meaning most treatment has very has a very narrow therapeutic index
we tend to be able to detect cancers when they're about 2/3 of the way through their life-cycle (and then they have become very aggressive and more difficult to cure)


what is TNM staging? and why is it helpful?

T- primary tumour (T1 and T2 = clinically localised) (T3 and T4 = locally advanced) N- n0 no node involvement, n1 node involvement and then M

helpful for prognosis and deciding treatment


what is fractional kill hypothesis?

this states that chemotherapeutic agents kill the same fraction of cells each dosage regardless of the absolute number of cells within the population. meaning small tumours are easier to kill and eradicate than larger tumours


what is the basis of familial cancer?

this is inheriting one faulty allele of tumour suppressor genes (so that only only more faulty allele needs to be acquired for cancer to develop)
Rb - retinoblastoma
P53- Frauemni syndrome


why is each cancer cell genetically unique?

despite cancer cell have characteristic mutations (i.e. to tumour suppressor genes and oncogenes) but the genetic permutations leads to those mutations can vary dramatically. furthermore because one gene can have many functions - depending on where the mutation is this can lead to certain loss of function and retention of others


what is the curable treatment for metastatic testicular cancer?



what is the main definitive difference between neo-adjuant and adjuvant therapy

adjuvant therapy is given post primary treatment
neo-adjuvant therapy is given before primary therapy


what is the purpose of adjuvant therapy?

it increases the chance of disease free survival after primary therapy. usually by killing small metastatic tumour cells which are too small to be detected


why do patients survive cancer?

because it is slow growing - patients can die of another cause
sensitivity of localised cancers to chemotherapy and radiotherapy
eradication of the cancer with adjuvant therapy


why do patients survive cancer?

because it is slow growing - patients can die of another cause
sensitivity of localised cancers to chemotherapy and radiotherapy
eradication of the cancer with adjuvant therapy


what is the infiltration of tumour cells by T-lymphocytes associated with?

infiltration with Treg: poor prognosis - because cannot mount an immune response against that tumour cell

infiltration with CD8+: better prognosis and also response to treatment

key point: not all lymphocyte infiltration has the same affect


what is meant by the equilibrium state?

this is the state at which most patients present to the clinic:
- it is when the immune system and the tumour are in balance with each other


what is meant by the escape state?

this is when the tumour is no longer kept in 'check' by the immune system and is actively proliferating. the immune response is no longer effective in controlling or mounting a response against the tumour


what are mutations with CTLA-4 associated with?

lymphoproliferative disorder

the CTLA-4 binds to CD80/CD86 on APC and this induces anergy in the T-cell.

CTLA-4 is also expressed by T-reg


what co-inhibitory molecules are involved in immune regulation?



what are the cytokine dependant mechanisms Treg use?

IL-10 and TFG-B1


what are the cytokine independent mechanisms Treg use?

Granzyme B


what is the effect of an unmanipulated immune system in tumours?

low CD28/foxp3 RATIO

- what this means is that the effector aspect of the immune system is highly suppressed. recall it is almost impossible to mount an immune response against a tumour with Treg cells


explain the mechanism underlying the Gvax-Anti CTLA-4 combination therapy?

Gvax: this is GS-CMF (and contains tumour antigens) this primers T-cells in the intra-tumour environment, and it also increases recruitment of APC into the tumour

Anti-CTLA-4 this activates the T-cells already within the tumour, and causes their proliferation

this therapy has no effect on Treg cells.

this combination therapy causes a shift in the CD8/FOXp3 ratio


explain the logic behind developing anti PD-1 antibodies such as Nivolumab?

a CD8+ infiltrates a tumour it secretes IFN-Y. this is detected by tumour cells which start increasing their expression of PD1-L.

PD1-L binds to PD-1 on the T-cells and this induces their anergy. if we prevent this binding the T-cells should respond to the tumour rather than be inactivated. PD-1 inactivation is specific to the tumour micro-enviroment. or in other words PD-1 is a check-point inside the tumour micro-environment


CTLA-4 and PD-1 modulate different aspects of the T-cell response: explain

CTLA-4: this is involved in regulating the activation of T-cell after they have been activated by APC in the lymphoid tissue (responsible for the activation phase)

PD-1: this is involved in regulating the activation of the T-CELL after they have been activated in secondary lymphoid tissue or within the tumour environment (Responsible for the effector phase)


how can antibodies act as anti-cancer drugs?

mAb binding can inhibit the receptor dimerisation required for activation of intracellular cascades

mAb binding can inhibit ligand binding

mAb binding can lead to activation of complement, and lead to complement dependant cytotoxicity

mAb binding can lead to antibody dependant cellular cytotoxicity (usually by recruiting by macrophages)


what mediates antibody dependant cellular cytotoxicity


usually this Fc gamma receptor is found on the surface of macrophages


how does an antibody activate the complement cascade?

by its Fc region binding to C1q -R


what is the function of FcRN

This increases the half life of an antibody by binding to Fc region of an antibody found within an endosome and recycle it to the more alkaline pH of the blood- preventing its intracellular degradation


what is the problem with using mouse mAb?

they're immunogenic and they're rapidly cleared from circulation