BORIIIING...

while waiting for Greece...

first, a bit of background

BCRA1 repairs DNA damage

in people with harmful BRCA1 mutation, damaged DNA goes unrepaired -- increasing cancer risk

breast, ovarian cancers are mostly BRCA1 cancers

cancer cells also use BRCA1 to repair damage. with faulty BRCA1, cancer cells rely on something called PARP to repair damage

so a treatment for BRCA1 cancers is to use PARP inhibitors

by inhibiting PARP, you take away the only other option for cancer cells to repair damage so damage accumulates in cancer cells and they die

not all cancers have BRCA1 mutation so PARP inhibitors are not effective in all cancers

scientists have found a way around that

they targeted something called Cdk1

BRCA1 is dependent on Cdk1. when you block Cdk1, BRCA1 becomes compromised

blocking Cdk1 in non-BRCA1 cancer turns the non-BRCA1 cancer into BRCA1 cancer making it susceptible to PARP inhibitors

scientists blocked Cdk1 and at the same time used a PARP inhibitor

they were able to shrink tumors

Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition : Nature Medicine : Nature Publishing Group

Cells that are deficient in homologous recombination, such as those that lack functional breast cancer–associated 1 (BRCA1) or BRCA2, are hypersensitive to inhibition of poly(ADP-ribose) polymerase (PARP). However, BRCA-deficient tumors represent only a small fraction of adult cancers, which might restrict the therapeutic utility of PARP inhibitor monotherapy. Cyclin-dependent kinase 1 (Cdk1) phosphorylates BRCA1, and this is essential for efficient formation of BRCA1 foci. Here we show that depletion or inhibition of Cdk1 compromises the ability of cells to repair DNA by homologous recombination. Combined inhibition of Cdk1 and PARP in BRCA–wild-type cancer cells resulted in reduced colony formation, delayed growth of human tumor xenografts and tumor regression with prolonged survival in a mouse model of lung adenocarcinoma. Inhibition of Cdk1 did not sensitize nontransformed cells or tissues to inhibition of PARP. Because reduced Cdk1 activity impaired BRCA1 function and consequently, repair by homologous recombination, inhibition of Cdk1 represents a plausible strategy for expanding the utility of PARP inhibitors to BRCA-proficient cancers.