What is a PARP Inhibitor? | Dana-Farber Cancer Institute | Science Illustrated

Just like normal cells, cancer cells have ways of repairing damage that occurs to them. In this episode of Science Illustrated we discuss one way, scientists are able to attack some cancers by preventing cancer cells from repairing themselves.
For more information on PARP Inhibitors, visit: www.dana-farber.org/PARP-inhib...
Transcript:
Every cell in our body is a machine with a special function. And, like machines everywhere, our cells sometimes suffer damage that interferes with their operation.
One part of a cell that can be damaged is DNA, the genetic material that controls just about everything a cell does. Fortunately, cells have several mechanisms for making repairs. When both strands of the DNA molecule are damaged, normal cells use genes known as BRCA1 and BRCA2 to create proteins that help repair the breaks.
Cancer cells, too, have ways of repairing damage to their DNA, which allows them to continue wreaking havoc within the body.
In some cancer patients, however, mutations in the BRCA genes prevent the proteins from making repairs. Without repairs, damage would pile up to the point where DNA could no longer function, and the cancer cells would die.
But cancer cells have a second repair crew that specializes in fixing damaged DNA. The crew is led by proteins known as poly ADP ribose polymerases, or PARPs. These repairs allow the cancer cells to remain alive and to grow and divide.
Now, doctors have a new way of attacking such cells. Drugs known as PARP inhibitors can knock the PARP proteins out of commission.
The loss of the PARP repair crew allows more and more damage to occur to the cancer cells’ DNA.
Eventually the DNA becomes so damaged it’s useless, and the cancer cells die.

[@Ann-np3mv]

love the animation, clears things up. Thank you!

[@blenli]

I finally understand this concept, thank you so much!

[@gshivashimpi77]

So simple explanation to understand the concept. Thank you

[@systemscholar]

If we inhibit PARP don't we also inhibit the repair of healthy cells - which could lead to more cancer?

[@danielgladish2502]

I think the rationale is that you have redundancy because normal cells have functional BRCA1/2 proteins and are thus able to compensate for the loss of PARP activity

[@PaygeFan]

this is late, but PARP inhibitors only affect BRCA1-/BRCA2- (BRCA deficient cells). BRCA deficient cells lack homologous recombination DNA repair mechanisms, so when we use PARP inhibitors, we prevent PARP from fixing nicks in single stranded DNA. Therefore, these BRCA- cells cannot fix the ssDNA break and these breaks become dsDNA breaks, and since the BRCA- cells also cannot use homologous recombination to fix those dsDNA breaks, the cells arrest in the cell cycle and apoptosis occurs.

[@ds6205]

So if we don’t use parp inhibitors, parp will continue to repair the cancerous cells?

[@jieyawu2424]

Thank you! The animation is so cute and vivid~

[@haroonfarooq1987]

So easy to understand. Thanks

[@ghaidaal-hashmi887]

Such a lovely video thank you very much! god bless you

[@sethkinda354]

much thanks for the clear explanation..

[@chandranimitra1059]

It’s so nicely explained....

[@chrisf6838]

Easy to understand.

[@explorewithhamzi]

Thank you so much, made easy.

[@jennifermcclendon1043]

Very well done!

[@doctorzee8007]

An Amazing explanation

[@clar4011]

Had an exam about this two weeks ago, wished I had stumbled upon this earlier

[@aquila1722]

good animation to teach easily👍🏻

[@nomalevolence]

very well made!

[@abhisek175]

Great animation

[@barkhasaraswat6956]

superrrrbbb ................easy to understand

[@Turokzp7777]

Thank you a lot!!!

[@salmonflavored]

A) excellent presentation of the mechanism; B) this lady needs to start an ASMR channel

[@YapaWijeratne]

Wow. Thank you

[@fieldtripinmyparty]

simply perfect

[@sushmadontaraboina548]

THANK YOU

[@scorpiolove3049]

Beautiful

[@bayupharmd1773]

nice info

[@user-fc7oi9mx7g]

Thank you

[@magykimo3325]

Waaaaw i spend two days to know what PARP IS its beneficial for visual learners

[@leduong5132]

the video image is too poor, you need to fix it more

[@battmannt]

Do PARP cells have any benefit to the DNA? If so what happens to the DNA needing to repair itself if the PARP all dies?

[@ThatSecondDude]

PARP is a repair mechanism for single stranded breaks. BRCA is a repair mechanism for double stranded breaks. single stranded breaks become double stranded breaks. If you have one or the other, it gets fixed. Normal (noncancer) cells have working BRCA, so if you kill the PARP, they still work. Cancer cells don't have working BRCA, so if you kill the PARP, it dies.

[@sreenbs]

@@ThatSecondDude im still a bit confused. correct me if i am wrong. BRCA MT causes failure to repair DSB and this leads to cell death. which Im assuming is great since cancerous cells are dying. why would we need parp-i when BRCA MT can already to that job ie causing cell death?

[@Littleprinceleon]

@@sreenbs most likely some salvage pathway(s) to Brca1/2...

[@ievavain]

@@sreenbs from what i was taught, BRCA is almost like a backup for PARP; the way I see it is that PARP is a repair mechanism for smaller errors and therefore prevents it from becoming a bigger issue (like double stranded breaks, where BRCA is needed). also having 2 systems that are able to fix DNA is advantageous anyways as it would take so much more mutations to actually affect both systems. people who have brca1/2 mutations are already more susceptible to certain cancers because there is more chance for mutation due to there being one less system that fixes DNA damage, however treating cancer in these people also gives way to knocking out the main system that BRCA-deficient cells rely on for DNA repair - PARP. eliminating their main remaining way of repair would kinda finish them off.
I guess the point is that lack of BRCA does not necessarily cause cell death as it still uses PARP for repair, therefore to finish the cell off, both mechanisms are ideally not active. hope this helps!

[@kicaj741]

Cool, but what about non cancer, 99-95 percent of your body cels? they are gone too, arent they?

[@dr.s.naseriniaki1660]

Just understand why its repair is not beneficial, Thanks a lot.

[@wegg4730]

PAAAARRRRRP

[@ShepvasNormandy]

It's a little scary to see a bunch of dead PARP dudes >_< wish they would have used something a little more scary to represent PARP.

[@olddog2706]

cutee

[@bibinkanjirathingal]

Easy to understand .