Cancer has long been an enemy for humans. In fact too long to be honest.
It's time that cancer gets a dose of its own medicine - time for cancer to get scared and I'll tell you why.
In a normal cell there are 2 DNA repair pathways; BRCA1 and BRCA2 are human genes that refer to a class known as tumor supressor genes.
Mutations in these have been linked to breast and ovarian cancer.
The concept of synthetic lethality is linked to the DNA repair pathways.
Loss of functional BRCA1/2 affects the choice of DNA double strand break repair pathway (DSB). In normal cells DNA DSB's are repaired by homologous recombination.
Functional BRCA1/2 are needed for repair by homologous recombination and genomic stability.
In the absence (due to mutations) of these genes an alternative repair pathway is used such as non-homologous end joining (NHEJ) and single strand annealing (SSA) which leads to to:
- cell death
- cell survival with genomic instability
The concept of synthetic lethality is that when a mutation occurs in either of the 2 genes has no effect but combining the 2 genes leads to the death of that cell.
In cancer therapy this means inhibiting one of these genes where the other is defective.
BRCA and PARP are involved in DNA repair. In cancer cells without the BRCA gene a PARP inhibitor should be used to cause cell death.
This should be selectively lethal to tumour cells but not to normal cells.
It's time that cancer gets a dose of its own medicine - time for cancer to get scared and I'll tell you why.
From the Journal of Clinical Oncology:
These refer mainly to ovarian and breast cancers:In a normal cell there are 2 DNA repair pathways; BRCA1 and BRCA2 are human genes that refer to a class known as tumor supressor genes.
Mutations in these have been linked to breast and ovarian cancer.
The concept of synthetic lethality is linked to the DNA repair pathways.
Loss of functional BRCA1/2 affects the choice of DNA double strand break repair pathway (DSB). In normal cells DNA DSB's are repaired by homologous recombination.
Functional BRCA1/2 are needed for repair by homologous recombination and genomic stability.
In the absence (due to mutations) of these genes an alternative repair pathway is used such as non-homologous end joining (NHEJ) and single strand annealing (SSA) which leads to to:
- cell death
- cell survival with genomic instability
The concept of synthetic lethality is that when a mutation occurs in either of the 2 genes has no effect but combining the 2 genes leads to the death of that cell.
In cancer therapy this means inhibiting one of these genes where the other is defective.
BRCA and PARP are involved in DNA repair. In cancer cells without the BRCA gene a PARP inhibitor should be used to cause cell death.
This should be selectively lethal to tumour cells but not to normal cells.
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